Cancer continues to be among the most substantial health challenges globally. Among various natural compounds, berberine, an isoquinoline alkaloid obtained from Coptidis Rhizoma, has garnered considerable attention for its broad-spectrum biological activities, including anti-inflammatory, antioxidant, anti-diabetic, anti-obesity, and anti-microbial activities. Furthermore, berberine exhibits a broad spectrum of anti-cancer efficacy against various malignancies, such as ovarian, breast, lung, gastric, hepatic, colorectal, cervical, and prostate cancers. Its anti-cancer mechanisms are multifaceted, encompassing the inhibition of cancer cell proliferation, the prevention of metastasis, the induction of apoptosis, the facilitation of autophagy, the modulation of the tumor microenvironment and gut microbiota, and the enhancement of the efficacy of conventional therapeutic strategies. This paper offers an exhaustive overview of the cancer-fighting characteristics of Coptidis Rhizoma and berberine, while also exploring recent developments in nanotechnology aimed at enhancing the bioavailability of berberine. Furthermore, the side effects and safety of berberine are addressed as well. The potential role of artificial intelligence in optimizing berberine's therapeutic applications is also highlighted. This paper provides precious perspectives on the prospective application of Coptidis Rhizoma and berberine in the prevention and management of cancer.

Phellodendri cortex (PC), the dried trunk bark of Phellodendron amurense RUPR, has traditionally been used to treat patients who suffer from gastroenteritis, abdominal pain or diarrhea. Its major bioactive compounds include alkaloids and limonin, and many physiological activities including anti-microbial, anti-ulcer and anti-cancer as well as anti-inflammation have been reported. Although PC is an effective anti-inflammatory natural substance that inhibits the inflammatory response, its effect on allergic asthma has not yet been investigated. The aim of this study was to evaluate the anti-asthmatic effects of PC in an ovalbumin (OVA)-induced murine model of asthma. As a result, PC inhibited airway eosinophil accumulation, the influx of inflammatory cells, airway hyperresponsiveness (AHR), production of Th2 cytokines (IL-4, IL-5 and IL-13) and tumor necrosis factor-α (TNF-α) in the bronchoalveolar lavage fluid and/or lung, as well as OVA-specific immunoglobulin E (IgE) in the serum. Furthermore, PC suppressed the gene expression of IL-4, IL-5, IL-13, TARC and CCR3, and attenuated unique histological changes that are associated with airway inflammatory reactions including the infiltration of various inflammatory cells, collagen deposition and goblet cell hyperplasia in lung tissues. These results indicate that PC may have preventive and/or therapeutic effects for allergic asthma via the inhibition of cytokines, chemokines and chemokine receptors associated with allergic inflammation.

The isoquinoline alkaloid berberine, a bioactive compound derived from various plants, has demonstrated extensive therapeutic potential. However, its clinical application is hindered by poor water solubility, low bioavailability, rapid metabolism, and insufficient targeting. Metal-based nanoplatforms offer promising solutions, enhancing drug stability, controlled release, and targeted delivery. This review comprehensively explores the synthesis, physicochemical properties, and biomedical applications of metal-based nanocarriers, including gold, silver, iron oxide, zinc oxide, selenium, and magnetic nanoparticles, for berberine delivery to improve berberine's therapeutic efficacy. Recent advancements in metal-based nanocarrier systems have significantly improved berberine delivery by enhancing cellular uptake, extending circulation time, and enabling site-specific targeting. However, metal-based nanoplatforms encounter several limitations of potential toxicity, limited large-scale productions, and regulatory constraints. Addressing these limitations necessitates extensive studies on biocompatibility, long-term safety, and clinical translation. By summarizing the latest innovations and clinical perspectives, this review aims to guide future research toward optimizing berberine-based nanomedicine for improved therapeutic efficacy.

Berberine has been widely studied for its biological functions in various diseases, including cancer, diabetes, and cardiovascular diseases. Nevertheless, structural modifications of berberine have been demonstrated to augment its pharmacological efficacy in specific biological processes, particularly osteogenesis. In this study, we aimed to explore new berberine derivatives with pro-osteogenic activity and molecular mechanisms. Our results demonstrated that compound 13 is the most effective among the tested compounds. Compound 13 significantly enhanced BMP4-induced alkaline phosphatase (ALP) staining and increased the transcriptional activity of osteogenic markers such as ALP, Runt-related gene 2 (Runx2), and Osterix at both the mRNA and protein levels. Furthermore, we found that the Akt and PKC signaling pathways play crucial roles in compound 13-induced osteogenesis via treatment with specific inhibitors. The molecular docking results supported the potential interaction between compound 13 and these kinases. These findings highlighted the regulatory role of compound 13 in osteoblast differentiation via the Akt and PKC signaling pathways. Overall, our study provides compelling evidence that compound 13 is a promising therapeutic candidate for the treatment of osteoporosis, with the potential for further development and optimization to improve bone health and strength.

This study aimed to enhance the antibacterial efficacy of BBR, a natural alkaloid with limited bioavailability and solubility, by encapsulating it in niosomes using saponin as a biosurfactant. Niosomes, non-ionic surfactant-based vesicles, improve drug stability and targeted delivery. The niosomes were synthesized using a ball milling-assisted method to optimize particle size and encapsulation efficiency. The formulation was characterized for particle size, zeta potential, encapsulation efficiency, and release kinetics. Niosomes with saponin had a particle size of 185 nm, a negative zeta potential, and the slowest release rate, following the Higuchi model. BBR-loaded niosomes achieved impressive entrapment efficiency (E.E%) of up to 93.7. The addition of saponin was expected to boost the antibacterial effects through synergistic mechanisms. The antibacterial efficacy of the formulation was assessed against Staphylococcus aureus and Escherichia coli. The resulting niosomal formulation exhibited significantly improved antibacterial activity compared to free BBR. The minimum bactericidal concentration (MIC) of the niosomes containing saponin (NSa2) and BBR against S. aureus and E. coli was found to be 0.08 ± 0.0 mg/ml. In contrast, the MBC of BBR alone against S. aureus was 0.24 ± 0.02 mg/ml, while for E. coli, it was 0.25 ± 0.02 mg/ml. These findings suggest that this niosomal formulation could be a promising approach for delivering BBR with improved therapeutic efficiency.

Although berberine (BBR) is well known as an active constituent in traditional medicines used in the treatment of gastrointestinal diseases, its potential against viral gastroenteritis has not been specifically reported. This study aims to investigate the antiviral activity of BBR against rotavirus and evaluate its cytotoxicity and pharmacological efficacies, including antioxidant and anti-inflammatory activities in vitro. Using ultraviolet-visible absorption spectroscopy, the saturation concentration of BBR was determined as 2261 μg/mL, indicating that BBR is a poor water-soluble compound. The inhibition rate of nitric oxide (NO) production of BBR solution at a concentration of 283 μg/mL was similar to that of Cardamonin 0.3 μM with a cell viability of 92.46±0.35 %, revealing the anti-inflammatory activity of BBR. The cytotoxicity of the BBR solution depended on its concentration, whereby the 50 % cytotoxicity concentration (CC50) of BBR after 96 h exposure was 664 μg/mL. Investigation of cytopathic effects (CPEs) of MA104 cells treated with BBR and BBR-incubated rotavirus indicates that BBR could effectively inhibit the replication of rotavirus. CPEs were not observed in the cells inoculated with rotavirus (100TCID50) which was pre-incubated with BBR for 96 hours at a BBR concentration of 283 μg/mL. Therefore, the study provides reliable results to demonstrate the ability of BBR to inhibit the replication of rotavirus.

Despite the remarkable biological effects of berberine (BBR), particularly on fertility, its bioavailability is low. This study aims to test the effectiveness of novel nanostructured biloalbuminosomes (BILS) of BBR and its metabolite berberrubine (M1) in treatment of testicular and prostatic lesions. M1 was semi-synthesized from BBR using microwave-assisted reaction. The solvent evaporation method was used to prepare BBR-BILS and M1-BILS by three different concentrations of sodium cholate (SC) or glycocholate (SG), along with the incorporation of bovine serum albumin (BSA). The prepared BILS were fully characterized. Male infertility was induced by cadmium (Cd) at 5 mg/kg and lead (Pb) at 20 mg/kg contaminated water for 90 days, followed by treatment with BBR, M1, and their BILS (BBR-BILS and M1-BILS) for 45 days. Blood male infertility markers, testicular and prostatic oxidative stress status, autophagy, inflammation, along with testicular and prostatic concentrations of Cd and Pb, and histopathology of both tested tissues were determined using standardized protocols. The optimal BBR-BILS and M1-BILS nano-preparations, containing 30 mg SC, were chosen based on the best characterization properties of the preparations. Both nano-preparations improved heavy metals-induced testicular and prostatic deformities, as they reduced Bax and elevated Bcl-2 expressions in both tissues. Moreover, they activated the mTOR/PI3K pathway with a marked reduction in AMPK and activated LC-3II protein levels. Consequently, testicular and prostatic architecture and functions were improved. This study is the first to report the preparation of BBR and M1 BILS nano-preparations and proved their superior efficacy compared to free drugs against testicular and prostatic deformities by attenuating oxidative stress-induced excessive autophagy, offering a new hope to manage male infertility.

Berberine is a promising bioactive compound that has gained great attention against numerous diseases but its low solubility and poor systemic bioavailability hinders its clinical applicability. Therefore, this study attempted to enhance the therapeutic potential of berberine by its nanoencapsulation. Berberine loaded guar-acacia gum nanocomplexes (Ber/Gu-AGNCs) were prepared by ionic complexation method; characterized and evaluated for anti-obesity activity in high fat diet (HFD) induced obese rats. HFD was given to animals for 6 consecutive weeks. Orlistat (20 mg/kg, p.o.), berberine (10 mg/kg), Ber/Gu-AGNCs (10 and 20 mg/kg, p.o) and Gu-AGNCs (blank) were administered once a day after giving HFD for 6 weeks; and continued up to 12 weeks along with HFD. Obesity was evaluated by the measurement of morphological parameters, blood glucose, serum lipid profiles, liver enzymes and levels of oxidative stress markers. Moreover, histopathological studies of liver and adipose tissue were also carried out. The results showed that Ber/Gu-AGNCs exhibited spherical morphology and narrow size distribution. In addition, Ber/Gu-AGNCs were significantly more effective in controlling the body weight, body mass index (BMI), adiposity index, liver index, blood glucose levels, serum lipids and oxidative stress levels in comparison to berberine in HFD-induced obese rats. Furthermore, histopathological examination of liver and adipose tissue revealed the anti-obesity effect of Ber/Gu-AGNCs (10 and 20 mg/kg), as indicated by decrease in hepatosteatosis and inflammation in liver tissue; and decrease in the size of adipocytes in fat depots. Thus, nanoencapsulation of berberine into gum nanocomplexes displayed better anti-obesity activity when compared to free berberine.

Berberine, an isoquinoline alkaloid, is known for anti-inflammatory activities. However, the research on the anti-inflammatory mechanism of berberine is not comprehensive. Recently, studies have shown that MrgprB2 (Mas-related G-protein-coupled receptor B2) in mice and MrgprX2 (Mas-related G-protein-coupled receptor X2) in humans play vital roles in inflammation. Therefore, this study aims to investigate whether the anti-inflammatory activity of berberine is related to MrgprB2 receptor.

The anti-inflammatory activity of BH (berberine hydrochloride) was evaluated by hindpaw edema analysis, pathological analysis and RT-qPCR. Transgenic mice (MrgprB2-/- mice), HEK293T cell transfection, calcium imaging, electrophysiology, molecular docking and other methods were employed to investigate the potential relationship between the anti-inflammatory activity of BH and the MrgprB2 receptor.

The results demonstrated that BH significantly alleviated C48/80 (compound 48/80)-induced local inflammation in vivo. This was evidenced by a decrease in paw edema, reduced infiltration of inflammatory cells, inhibition of mast cell activation, and down-regulation of inflammatory factors such as CXCL13 (CXC subfamily 13) and TNF-α (tumor necrosis factor-α). It was also found that knockout of MrgprB2 receptor could block the anti-inflammatory activity of BH in mice. Furthermore, calcium imaging revealed that BH effectively inhibited the activity of MrgprB2 receptor in overexpressed HEK293T cells in vitro. Additionally, it was observed that BH also inhibited MrgprB2-mediated voltage-dependent current changes in mouse peritoneal mast cells. Molecular docking results further indicated that BH had affinity with MrgprX2 protein.

The anti-inflammatory mechanism of BH may be partially attributed to the inhibition of MrgprB2 receptor-mediated mast cell activation.

Lung cancer is the most fatal cancer worldwide. The etiology of lung cancer has yet to be fully characterized. Smoking and air pollution are several risk factors for lung cancer. Berberine, an isoquinoline alkaloid, is an antihyperglycemic, antidepressant, antioxidative, anti-inflammatory, and anticancer compound. Evidence substantiates that berberine has antitumor effects, exerting its effects by targeting a variety of cellular and molecular processes, such as apoptosis, autophagy, cell cycle arrest, migration, and metastasis. Although the beneficial effects of berberine have been reported, some limitations including low bioavailability and absorption as well as poor aqueous solubility have hindered its clinical application. Nanotechnology and nanodelivery bioformulation approaches may bypass these limitations. In addition, the combination of berberine with other therapies has been shown to result in greater treatment efficacy for lung cancer. Herein, we summarize cellular and molecular pathways that are affected by berberine, its clinical efficacy upon various combinations, and the potential for nanotechnology in lung cancer therapy.

Herbal medicines (HMs) have deciphered indispensable therapeutic effects against cardiovascular disease (CVD) (the predominant cause of death worldwide). The conventional CVD therapy approaches have not been efficient and need alternative medicines. The objective of this study was a review of herbal bioactive compound efficacy for CVD therapy based on computational and in silico studies. HM bioactive compounds with potential anti-CVD traits include campesterol, naringenin, quercetin, stigmasterol, tanshinaldehyde, Bryophyllin A, Bryophyllin B, beta-sitosterol, punicalagin, butein, eriodyctiol, butin, luteolin, and kaempferol discovered using computational studies. Some of the bioactive compounds have exhibited therapeutic effects, as followed by in vitro (tanshinaldehyde, punicalagin, butein, eriodyctiol, and butin), in vivo (gallogen, luteolin, chebulic acid, butein, eriodyctiol, and butin), and clinical trials (quercetin, campesterol, and naringenin). The main mechanisms of action of bioactive compounds for CVD healing include cell signaling and inhibition of inflammation and oxidative stress, decrease of lipid accumulation, and regulation of metabolism and immune cells. Further experimental studies are required to verify the anti-CVD effects of herbal bioactive compounds and their pharmacokinetic/pharmacodynamic features.

Phellodendron chinense C.K.Schneid(P. chinense Schneid) is known in TCM as Huang Bo, is traditionally used to support gastrointestinal function and alleviate stomach-related ailments, including gastric ulcer bleeding and symptoms of gastroesophageal reflux disease. Helicobacter pylori (H. pylori) is classified by the WHO as a Group 1 carcinogen. However, the specific activity and mechanism of action of P. chinense Schneid against H. pylori infection remain unclear. It has been noted that Huangjiu processing may alter the bitter and cold properties of P. chinense Schneid, but its effect on antimicrobial activity requires further investigation. Additionally, it remains uncertain whether berberine is the sole antimicrobial active component of P. chinense Schneid.

This study aims to elucidate the anti-H. pylori infection activity of P. chinense Schneid, along with its mechanism of action and key antimicrobial active components.

Phytochemical analysis was carried out by UPLC-MS/MS. HPLC was employed to quantify the berberine content of the extracts. Antimicrobial activity was assessed using the micro broth dilution method. Morphology was observed using SEM. The impact on urease activity was analyzed through in vitro urease enzyme kinetics. RT-qPCR was employed to detect the expression of virulence genes, including adhesin, flagellum, urease, and cytotoxin-related genes. The adhesion effect was evaluated by immunofluorescence staining and agar culture.

P. chinense Schneid exhibited strong antimicrobial activity against both antibiotic-sensitive and resistant H. pylori strains, with MIC ranging from 40 to 160 μg/mL. Combination with amoxicillin, metronidazole, levofloxacin, and clarithromycin did not result in antagonistic effects. P. chinense Schneid induced alterations in bacterial morphology and structure, downregulated the expression of various virulence genes, and inhibited urease enzyme activity. In co-infection systems, P. chinense Schneid significantly attenuated H. pylori adhesion and urease relative content, thereby mitigating cellular damage caused by infection. Huangjiu processing enhanced the anti-H. pylori activity of P. chinense Schneid. Besides berberine, P. chinense Schneid contained seven other components with anti-H. pylori activity, with palmatine exhibiting the strongest activity, followed by jatrorrhizine.

This study sheds light on the potential therapeutic mechanisms of P. chinense Schneid against H. pylori infection, demonstrating its capacity to disrupt bacterial structure, inhibit urease activity, suppress virulence gene transcription, inhibit adhesion, and protect host cells. The anti-H. pylori activity of P. chinense Schneid was potentiated by Huangjiu processing, and additional components beyond berberine were identified as possessing strong anti-H. pylori activity. Notably, jatrorrhizine, a core component of P. chinense Schneid, exhibited significant anti-H. pylori activity, marking a groundbreaking discovery.

Atopic eczema patients exhibit high levels of Staphylococcus aureus (S. aureus) skin colonization. S. aureus can stimulate macrophages and the expression of proinflammatory cytokines. Berberine (BBR), an alkaloid, attenuates S. aureus toxin production. This study investigated if BBR suppressed bacterial growth and inflammatory response induced by eczema-patient-derived S. aureus using murine macrophage (RAW 264.7) and human monocyte cell lines (U937). RAW 264.7 and U937 were treated with BBR at different concentrations and stimulated with heat-killed S. aureus (ATCC #33591) or S. aureus derived from severe eczema patients (EC01-EC10), who were undergoing topical steroid withdrawal, for 24 h. TNF-α protein levels were determined by ELISA, gene expression by qRT-PCR, cell cytotoxicity by trypan blue excursion, and reactive oxygen species (ROS) levels by fluorometric assay. BBR showed a bacteriostatic effect in S. aureus (ATCC strain #33591 and clinical isolates (EC01-EC10) and suppressed TNF-α production in RAW 264.7 and U937 cells exposed to heat-killed S. aureus (ATCC and clinical isolates) dose-dependently without any cell cytotoxicity. BBR (20 µg/mL) suppressed >90% of TNF-α production (p < 0.001), downregulated genes involved in inflammatory pathways, and inhibited S. aureus ROS production in U937 and RAW 264.7 cells (p < 0.01). BBR suppresses S. aureus-induced inflammation via inhibition of TNF-α release, ROS production, and expression of key genes involved in the inflammatory pathway.

Oxidative stress is a key factor in the development of chronic diseases such as type 2 diabetes, cardiovascular diseases, and liver disorders. Antioxidant therapies that target oxidative damage show significant promise in preventing and treating these conditions. Berberine, an alkaloid derived from various plants in the Berberidaceae family, enhances cellular defenses against oxidative stress through several mechanisms. It activates the AMP-activated protein kinase (AMPK) pathway, which reduces mitochondrial reactive oxygen species (ROS) production and improves energy metabolism. Furthermore, it boosts the activity of key antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), thus protecting cells from oxidative damage. These actions make berberine effective in managing diseases like type 2 diabetes, cardiovascular conditions, and neurodegenerative disorders. Silymarin, a flavonolignan complex derived from Silybum marianum, is particularly effective for liver protection. It activates the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, enhancing antioxidant enzyme expression and stabilizing mitochondrial membranes. Additionally, silymarin reduces the formation of ROS by chelating metal ions, and it also diminishes inflammation. This makes it beneficial for conditions like non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disorders. This review aims to highlight the distinct mechanisms by which berberine and silymarin exert their antioxidant effects.

According to the "cancer stem cell" (CSCs) theory, tumors are a diverse and expanding group of malignant cells that originate from a small number of CSCs. Despite treatment, these cells can still become active and proliferate, which can result in distant metastasis and local recurrences. A new paradigm in cancer treatment involves targeting both CSCs and the cancer cells in a tumor. This review aims to examine the literature on methods published to overcome chemoresistance due to the presence of CSCs in head and neck cancers. The review was registered with PROSPERO (ID# CRD42024512809). After Pub Med, Scopus, and WoS database searches, 31 relevant articles on oral squamous cell carcinoma (OSCC) were selected. Compounds that increased chemosensitivity by targeting CSCs in head and neck squamous cell carcinoma (HNSCC) were divided into (1) natural products, (2) adjuvant molecules to traditional chemotherapy, and (3) CSCs targeting patient-specific fresh biopsies for functional precision medicine.

This study investigated the antibacterial properties of Coptis rhizome, a plant traditionally used for respiratory infections, against Streptoccus pneumonia (S. pneumoniae), for which there has been minimal empirical evidence of effectiveness. The study particularly examined autolysis, indirectly associated with antibacterial resistance, when using Coptis rhizome for bacterial infections. In our methodology, Coptis rhizome was processed with ethanol and distilled water to produce four different extracts: CRET30, CRET50, CRET70, and CRDW. The antibacterial activity of these extracts were tested through Minimum Inhibitory Concentration (MIC) assays, disk diffusion tests, and time-kill assays, targeting both standard (ATCC 49619) and resistant (ATCC 70067) strains. The study also evaluated the extracts' biofilm inhibition properties and monitored the expression of the lyt gene, integral to autolysis. The results prominently showed that the CRET70 extract demonstrated remarkable antibacterial strength. It achieved an MIC of 0.125 µg/mL against both tested S. pneumoniae strains. The disk diffusion assay recorded inhibition zones of 22.17 mm for ATCC 49619 and 17.20 mm for ATCC 70067. Impressively, CRET70 resulted in a 2-log decrease in bacterial numbers for both strains, showcasing its potent bactericidal capacity. The extract was also effective in inhibiting 77.40% of biofilm formation. Additionally, the significant overexpression of the lytA gene in the presence of CRET70 pointed to a potential mechanism of action for its antibacterial effects. The outcomes provided new perspectives on the use of Coptis rhizome in combating S. pneumoniae, especially significant in an era of escalating antibiotic resistance.

Zinc oxide (ZnO) is frequently used in high concentrations to prevent diarrhea in weaning pigs. However, it can produce environmental pollution, because it is not absorbed by the intestines and is excreted in the feces. In studies to identify an alternative substance to ZnO, we used a model of colitis induced by dextran sulfate sodium (DSS) in rats to compare the anti-inflammatory effects of berberine with ZnO. DSS-treated rats displayed weight loss, shortening of the colon, increased fecal water content, and an increase in the disease activity index (DAI). In contrast, DSS + ZnO- and DSS + berberine-treated rats exhibited reduced colon shortening, decreased fecal water content, and a decrease in the DAI. Histological analysis revealed that both ZnO and berberine treatment reduced epithelial cell damage, crypt destruction, and infiltration of inflammatory cells. Moreover, the liver damage index was not significantly different between ZnO and berberine-treated rats. This study indicated that both ZnO and berberine can improve DSS-induced colitis in rats and suggests berberine as an alternative treatment to ZnO that would not cause environmental pollution.

Berberine (BBR), a widely used isoquinoline alkaloid derived from natural sources, exhibits aggregation-induced emission (AIE) characteristics and has biological applications such as in selective lipid droplet imaging and photodynamic therapy. However, natural BBR suffers from low fluorescence quantum yield (ΦF) and monotonous emission wavelength. In this paper, a series of C9-position-aryl-substituted berberine derivatives with a D-A structure were designed and synthesized. The electronic effect of the substitution groups can tune the intramolecular charge transfer (ICT) effect of the berberine derivatives, resulting in bluish green to NIR (508-682 nm) luminescence with AIE characteristics and enhanced ΦF up to 36% in the solid state. Interestingly, berberine derivatives containing an amino or a pyridyl group can exhibit fluorescence response to TFA. Cell imaging of the berberine derivatives was conducted using Caco-2 cancer cells, demonstrating their multi-color and efficient wash-free imaging capabilities. This work presents a new strategy for developing novel berberine derivatives with tunable AIE properties for application in biological imaging.

Berberis vulgaris (L.) has remarkable ethnopharmacological properties and is widely used in traditional medicine. The present study investigated B. vulgaris stem bark (Berberidis cortex) by extraction with 50% ethanol. The main secondary metabolites were quantified, resulting in a polyphenols content of 17.6780 ± 3.9320 mg Eq tannic acid/100 g extract, phenolic acids amount of 3.3886 ± 0.3481 mg Eq chlorogenic acid/100 g extract and 78.95 µg/g berberine. The dried hydro-ethanolic extract (BVE) was thoroughly analyzed using Ultra-High-Performance Liquid Chromatography coupled with High-Resolution Mass Spectrometry (UHPLC-HRMS/MS) and HPLC, and 40 bioactive phenolic constituents were identified. Then, the antioxidant potential of BVE was evaluated using three methods. Our results could explain the protective effects of Berberidis cortex EC50FRAP = 0.1398 mg/mL, IC50ABTS = 0.0442 mg/mL, IC50DPPH = 0.2610 mg/mL compared to ascorbic acid (IC50 = 0.0165 mg/mL). Next, the acute toxicity and teratogenicity of BVE and berberine-berberine sulfate hydrate (BS)-investigated on Daphnia sp. revealed significant BS toxicity after 24 h, while BVE revealed considerable toxicity after 48 h and induced embryonic developmental delays. Finally, the anticancer effects of BVE and BS were evaluated in different tumor cell lines after 24 and 48 h of treatments. The MTS assay evidenced dose- and time-dependent antiproliferative activity, which was higher for BS than BVE. The strongest diminution of tumor cell viability was recorded in the breast (MDA-MB-231), colon (LoVo) cancer, and OSCC (PE/CA-PJ49) cell lines after 48 h of exposure (IC50 < 100 µg/mL). However, no cytotoxicity was reported in the normal epithelial cells (HUVEC) and hepatocellular carcinoma (HT-29) cell lines. Extensive data analysis supports our results, showing a significant correlation between the BVE concentration, phenolic compounds content, antioxidant activity, exposure time, and the viability rate of various normal cells and cancer cell lines.

Berberine was identified in extracts of Berberis ruscifolia Lam., a plant used in traditional medicine as an analgesic. Its presence may be involved in the reported pharmacological activity of this species. However, there is still a lack of scientific research concerning its analgesic activity in the peripheral nervous system.

To investigate Berb-induced antinociception in the formalin test and to evaluate several pathways related to its pharmacological antinociceptive effects in chemical models of nociception in mice.

The antinociceptive activity of Berb was assessed by inducing the paw licking in mice with different allodynic agents. In the formalin test, the antiedematous and antithermal effect of Berb was evaluated simultaneously in the same experiment. Other nociceptive behavior produced by endogenous [prostaglandin E2 (PGE2), histamine (His), glutamate (Glu) or bradykinin (BK)] or exogenous [capsaicin (Caps) and cinnamaldehyde (Cin)] chemical stimuli, and activators as protein kinase A (PKA) and C (PKC), were also evaluated.The in vivo doses for p.o. were 3 and 30 mg/kg.

Berb, at 30 mg/kg p.o., showed a significant inhibition of the nociceptive action in formalin in both phases being stronger at the inflammatory phase (59 ± 9%) and more active than Asp (positive control) considering the doses evaluated. Moreover, Berb inhibited the edema (34 ± 10%), but not the temperature in the formalin test. Regarding the different nociceptive signaling pathways evaluated, the most relevant data were that the administration of p.o. of Berb, at 30 mg/kg, caused significant inhibition of nociception induced by endogenous [His (72 ± 11%), PGE2 (78 ± 4%), and BK (51 ± 7%)], exogenous [Cap (68 ± 4%) and Cinn (57 ± 5%)] compounds, and activators of the PKA [(FSK (86 ± 3%)] and PKC [(PMA(86 ± 6%)] signaling pathway. Berb did not inhibit the nociceptive effect produced by Glu.

The present study demonstrated, for the first time, the potential of Berb in several nociceptive tests, with the compound present in B. ruscifolia contributing to the analgesic effect reported for this species.

The rising prevalence of drug-resistant bacteria underscores the need to search for innovative and nature-based solutions. One of the approaches may be the use of plants that constitute a rich source of miscellaneous compounds with a wide range of biological properties. This review explores the antimicrobial activity of seven bioactives and their possible molecular mechanisms of action. Special attention was focused on the antibacterial properties of berberine, catechin, chelerythrine, cinnamaldehyde, ellagic acid, proanthocyanidin, and sanguinarine against Staphylococcus aureus, Enterococcus spp., Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, Serratia marcescens and Pseudomonas aeruginosa. The growing interest in novel therapeutic strategies based on new plant-derived formulations was confirmed by the growing number of articles. Natural products are one of the most promising and intensively examined agents to combat the consequences of the overuse and misuse of classical antibiotics.

Purpose: This study aims to investigate the potential of Oregon grape root extracts to modulate the activity of P-glycoprotein. Methods: We performed 3H-CsA or 3H-digoxin transport experiments in the absence or presence of two sources of Oregon grape root extracts (E1 and E2), berberine or berbamine in Caco-2 and MDCKII-MDR1 cells. In addition, real time quantitative polymerase chain reaction (RT-PCR) was performed in Caco-2 and LS-180 cells to investigate the mechanism of modulating P-glycoprotein. Results: Our results showed that in Caco-2 cells, Oregon grape root extracts (E1 and E2) (0.1-1 mg/mL) inhibited the efflux of CsA and digoxin in a dose-dependent manner. However, 0.05 mg/mL E1 significantly increased the absorption of digoxin. Ten µM berberine and 30 µM berbamine significantly reduced the efflux of CsA, while no measurable effect of berberine was observed with digoxin. In the MDCKII-MDR1 cells, 10 µM berberine and 30 µM berbamine inhibited the efflux of CsA and digoxin. Lastly, in real time RT-PCR study, Oregon grape root extract (0.1 mg/mL) up-regulated mRNA levels of human MDR1 in Caco-2 and LS-180 cells at 24 h. Conclusion: Our study showed that Oregon grape root extracts modulated P-glycoprotein, thereby may affect the bioavailability of drugs that are substrates of P-glycoprotein.

As a growing direction, nano-based therapy has become a successful paradigm used to address the phytogenic delivery-related problems in overcoming multivirulent vancomycin-resistant Staphylococcus aureus (VRSA) infection.

Hence, our aim was to develop and assess a novel nanocarrier system (mesoporous silica nanoparticles, MPS-NPs) for free berberine (Free-BR) as an antimicrobial alkaloid against strong biofilm-producing and multi-virulent VRSA strains using in vitro and in vivo mouse model.

Our outcomes demonstrated vancomycin resistance in 13.7% of Staphylococcus aureus (S. aureus) strains categorized as VRSA. Notably, strong biofilm formation was observed in 69.2% of VRSA strains that were all positive for icaA gene. All strong biofilm-producing VRSA strains harbored a minimum of two virulence genes comprising clfA and icaA with 44.4% of them possessing all five virulence genes (icaA, tst, clfA, hla, and pvl), and 88.9% being multi-virulent. The study findings affirmed excellent in vitro antimicrobial and antibiofilm properties of BR-loaded MPS-NPs. Real-time quantitative reverse transcription PCR (qRT-PCR) assay displayed the downregulating role of BR-loaded MPS-NPs on strong biofilm-producing and multi-virulent VRSA strains virulence and agr genes in both in vitro and in vivo mice models. Additionally, BR-loaded MPS-NPs supplementation has a promising role in attenuating the upregulated expression of pro-inflammatory cytokines' genes in VRSA-infected mice with attenuation in pro-apoptotic genes expression resulting in reduced VRSA-induced apoptosis. In essence, the current study recommends the future scope of using BR-loaded MPS-NPs as auspicious alternatives for antimicrobials with tremendous antimicrobial, antibiofilm, anti-quorum sensing (QS), and anti-virulence effectiveness against problematic strong biofilm-producing and multi-virulent VRSA-associated infections.

Antiretroviral therapy has increased the life expectancy of people living with HIV. However, this increase is not free of comorbidities, and metabolic syndrome is one of the most prevalent. Berberine is an alkaloid nutraceutical that has been shown to ameliorate metabolic disorders such as prediabetes, polycystic ovary syndrome, and non-alcoholic fatty liver disease. However, it has not been tested in HIV infection. Therefore, we conducted a randomized controlled trial to evaluate the efficacy of berberine in improving metabolic syndrome.

In this double-blind, placebo-controlled trial, adults living with HIV under virological suppression and metabolic syndrome received either berberine 500 mg TID or placebo for 20 weeks. The primary outcomes were a composite of weight reduction, insulin resistance decrease, and lipid profile improvement. A total of 43 participants were randomized (22 in the berberine group and 21 in the placebo group); 36 participants completed the follow-up and were analyzed. The berberine group showed a reduction in weight and body mass index, lower insulin resistance, and a reduction in TNF-alpha. The control group had higher total cholesterol, c-LDL, and IL-6 concentration.

In people living with HIV under virological suppression, berberine was safe and improves clinical and biochemical components of metabolic syndrome. However, further studies with more participants and longer intervention periods need to be explored.

Berberine is an isoquinoline alkaloid naturally produced by several types of plants. Berberine has extensive pharmacological effects, such as anti-diabetic, anti-inflammatory, and antioxidant effects. In the current study, we assess the antinociceptive effects of berberine and its association with the l -arginine ( l -Arg)/NO/cGMP/K ATP channel pathway via intraplantar administration in rats. To examine the antinociceptive properties of berberine, the formalin test was conducted. The number of rat paw flinches was counted for an h. l -Arg (precursor of nitric oxide, 3-30  μ g/paw), l -NAME (NO synthase inhibitor, 10 and 100  μ g/paw), methylene blue (guanylyl cyclase inhibitor, 100 and 200  μ g/paw), and glibenclamide (ATP-sensitive potassium channel blocker, 10 and 30  μ g/paw) were locally injected, respectively, into the right hind paws of rats as a pre-treatment before berberine injection to understand how the l -Arg/NO/cGMP/K ATP pathway plays a role in the antinociceptive effect of berberine. The ipsilateral injection of berberine into the right paw (0.1-10 0   μ g/paw) showed a dose-dependent antinociceptive effect in both the first and second phases of the formalin test, almost similar to morphine (25  μ g/paw). Intraplantar injection of l -Arg (30 µg/paw) increased the antinociceptive effect of berberine in the second phase. In addition, injection of l -NAME, methylene blue, and glibenclamide caused a reduction in the antinociceptive effect of berberine throughout the second phase in a dose-dependent manner. However, the antinociceptive effects of berberine in the first phase of the rat formalin test were not affected by this pathway. As a novel local antinociceptive agent, berberine can exert a peripheral antinociceptive effect via the l -Arg/NO/cGMP/K ATP channel pathway.

Traditional Chinese Medicines (TCMs) have been used for centuries for the treatment and management of various diseases. However, their effective delivery to targeted sites may be a major challenge due to their poor water solubility, low bioavailability, and potential toxicity. Nanocarriers, such as liposomes, polymeric nanoparticles, inorganic nanoparticles and organic/inorganic nanohybrids based on active constituents from TCMs have been extensively studied as a promising strategy to improve the delivery of active constituents from TCMs to achieve a higher therapeutic effect with fewer side effects compared to conventional formulations. This review summarizes the recent advances in nanocarrier-based delivery systems for various types of active constituents of TCMs, including terpenoids, polyphenols, alkaloids, flavonoids, and quinones, from different natural sources. This review covers the design and preparation of nanocarriers, their characterization, and in vitro/vivo evaluations. Additionally, this review highlights the challenges and opportunities in the field and suggests future directions for research. Nanocarrier-based delivery systems have shown great potential in improving the therapeutic efficacy of TCMs, and this review may serve as a comprehensive resource to researchers in this field.

Pain continues to be an enormous global health challenge, with millions of new untreated or inadequately treated patients reported annually. With respect to current clinical applications, opioids remain the mainstay for the treatment of pain, although they are often associated with serious side effects. To optimize their tolerability profiles, medicinal chemistry continues to study novel ligands and innovative approaches. Among them, natural products are known to be a rich source of lead compounds for drug discovery, and they hold potential for pain management. Traditional medicine has had a long history in clinical practice due to the fact that nature provides a rich source of active principles. For instance, opium had been used for pain management until the 19th century when its individual components, such as morphine, were purified and identified. In this review article, we conducted a literature survey aimed at identifying natural products interacting either directly with opioid receptors or indirectly through other mechanisms controlling opioid receptor signaling, whose structures could be interesting from a drug design perspective.

Airway remodelling occurs in chronic respiratory diseases (CRDs) such as asthma and chronic obstructive pulmonary disease (COPD). It is characterized by aberrant activation of epithelial reparation, excessive extracellular matrix (ECM) deposition, epithelial-to-mesenchymal transition (EMT), and airway obstruction. The master regulator is Transforming Growth Factor-β (TGF-β), which activates tissue repair, release of growth factors, EMT, increased cell proliferation, and reduced nitric oxide (NO) secretion. Due to its fundamental role in remodelling, TGF-β is an emerging target in the treatment of CRDs. Berberine is a benzylisoquinoline alkaloid with antioxidant, anti-inflammatory, and anti-fibrotic activities whose clinical application is hampered by poor permeability. To overcome these limitations, in this study, berberine was encapsulated in monoolein-based liquid crystalline nanoparticles (BM-LCNs). The potential of BM-LCNs in inhibiting TGF-β-induced remodelling features in human bronchial epithelial cells (BEAS-2B) was tested. BM-LCNs significantly inhibited TGF-β-induced migration, reducing the levels of proteins upregulated by TGF-β including endoglin, thrombospondin-1, basic fibroblast growth factor, vascular-endothelial growth factor, and myeloperoxidase, and increasing the levels of cystatin C, a protein whose expression was downregulated by TGF-β. Furthermore, BM-LCNs restored baseline NO levels downregulated by TGF-β. The results prove the in vitro therapeutic efficacy of BM-LCNs in counteracting TGF-β-induced remodelling features. This study supports the suitability of berberine-loaded drug delivery systems to counteract airway remodelling, with potential application as a treatment strategy against CRDs.

Venous thromboembolism is a very common and costly health problem. Deep-vein thrombosis (DVT) can cause permanent damage to the venous system and lead to swelling, ulceration, gangrene, and other symptoms in the affected limb. In addition, more than half of the embolus of pulmonary embolism comes from venous thrombosis, which is the most serious cause of death, second only to ischemic heart disease and stroke patients. It can be seen that deep-vein thrombosis has become a serious disease affecting human health. In recent years, with the deepening of research, inflammatory response is considered to be an important pathway to trigger venous thromboembolism, in which the transcription factor NF-κB is the central medium of inflammation, and the NF-κB signaling pathway can regulate the pro-inflammatory and coagulation response. Thus, to explore the mechanism and make use of it may provide new solutions for the prevention and treatment of thrombosis.

Hericium erinaceus, berberine, and quercetin are effective in experimental colitis. It is unknown whether they can ameliorate inflammatory bowel diseases in humans. This ex vivo study aimed to evaluate the anti-inflammatory potential of a nutraceutical compound of HBQ-Complex® (H. erinaceus, berberine, and quercetin), biotin, and niacin in inflammatory bowel disease patients. Tissue specimens were obtained either from Normal-Appearing Mucosa (NAM) or from Inflamed Mucosa (IM) in 20 patients with inflammatory bowel disease. mRNA and protein expression of COX-2, IL-10, and TNF-α were determined in NAM and IM biopsy samples (T0). IM samples were then incubated in HBQ-Complex® (with the addition of niacin and biotin), and COX-2, IL-10, and TNF-α tissue levels were evaluated at 120 minutes (T1) and 180 minutes (T2). Incubation with this compound resulted in a progressive decrease in gene and protein COX-2 and TNF-α expression at T1/T2 in the IM. IL-10 showed an opposite trend, with a progressive increase of mRNA and protein expression over the same time window. HBQ-Complex® (with the addition of niacin and biotin) decreased the expression of proinflammatory cytokines at the mRNA and protein levels in IBD tissue. On the contrary, mRNA and protein expression of the anti-inflammatory cytokine IL-10 showed a progressive increase.

Berberine (BBR) is a potential plant metabolite and has remarkable anticancer properties. Many kinds of research are being focused on the cytotoxic activity of berberine in in vitro and in vivo studies. A variety of molecular targets which lead to the anticancer effect of berberine ranges from p-53 activation, Cyclin B expression for arresting cell cycles; protein kinase B (AKT), MAP kinase and IKB kinase for antiproliferative activity; effect on beclin-1 involved in autophagy; reduced expression of MMP-9 and MMP-2 for the inhibition of invasion and metastasis etc. Berberine also interferes with transcription factor-1 (AP-1) activity responsible for the expression of oncogenes and neoplastic transformation of the cell. It also leads to the inhibition of various enzymes which are directly or indirectly involved in carcinogenesis like N acetyl transferase, Cyclo-oxygenase-2, Telomerase and Topoisomerase. In addition to these actions, Berberine plays a role in, the regulation of reactive oxygen species and inflammatory cytokines in preventing cancer formation. Berberine anticancer properties are demonstrated due to the interaction of berberine with micro-RNA. The summarized information presented in this review article may help and lead the researchers, scientists/industry persons to use berberine as a promising candidate against cancer.

Ulcerative colitis (UC) with continuous and extensive inflammation is limited to the colon mucosa and can lead to abdominal pain, diarrhea, and rectal bleeding. Conventional therapies are associated with several limitations, such as systemic side effects, drug degradation, inactivation, and limited drug uptake, leading to poor bioavailability. These restrictions necessitate drug delivery to the colon so that the drug passes through the stomach unchanged and has selective access to the colon. The present study aimed to formulate 5-aminosalicylic acid (5-ASA) and berberine (BBR) in chitosan nanoparticles cross-linked by HPMCP (hydroxypropyl methylcellulose phthalate) as a colon drug delivery system for UC. Spherical nanoparticles were prepared. They showed appropriate drug release in the simulated intestinal fluid (SIF), while the release did not occur in the simulated gastric fluid (SGF). They improved disease activity parameters (DAI) and ulcer index, increased the length of the colon, and decreased the wet weight of the colon. Furthermore, histopathological colon studies showed an improved therapeutic effect of 5-ASA/HPMCP/CSNPs and BBR/HPMCP/CSNPs. In conclusion, although 5-ASA/HPMCP/CSNPs showed the best effect in the treatment of UC, BBR/HPMCP/CSNPs, and 5-ASA/BBR/HPMCP/CSNPs were also effective in vivo study, and this study anticipated they could be helpful in future clinical applications for the management of UC.

The conventional method of applying local medications for treating wound infections is often ineffective because of the dilution of drugs by the excess wound exudate. In addition, there have been insufficient studies investigating the adhesion between drug-loaded nanomaterials and cells or tissue. To address this intractable problem, berberine-silk fibroin microspheres (Ber@MPs) with an extracellular matrix-anchoring function were developed in this study. The microspheres were prepared from silk fibroin using the polyethylene glycol emulsion precipitation method. Subsequently, berberine was loaded onto the microspheres. Our results revealed that Ber@MPs firmly anchored to cells, continuously releasing berberine in the microenvironment. Moreover, both Ber@MPs and Ber@MPs-cell complexes exerted a strong and long-lasting antibacterial effect against Staphylococcus aureus and Staphylococcus epidermidis in the microenvironment, despite the large amount of wound exudate. In addition, Ber@MPs effectively resisted the inflammatory response induced by lipopolysaccharides and accelerated the migration of fibroblasts and neovascularization of endothelial cells cultured in inflammation-induced media. Finally, the in vivo experiments confirmed that the Ber@MP spray accelerated the healing of infected wounds via its antibacterial and anti-inflammatory effects. Therefore, this study provides a novel strategy for treating infected wounds in the presence of excess exudate.

Chronic obstructive pulmonary disease (COPD) is an irreversible inflammatory respiratory disease characterized by frequent exacerbations and symptoms such as cough and wheezing that lead to irreversible airway damage and hyperresponsiveness. The primary risk factor for COPD is chronic cigarette smoke exposure, which promotes oxidative stress and a general pro-inflammatory condition by stimulating pro-oxidant and pro-inflammatory pathways and, simultaneously, inactivating anti-inflammatory and antioxidant detoxification pathways. These events cause progressive damage resulting in impaired cell function and disease progression. Treatments available for COPD are generally aimed at reducing the symptoms of exacerbation. Failure to regulate oxidative stress and inflammation results in lung damage. In the quest for innovative treatment strategies, phytochemicals, and complex plant extracts such as agarwood essential oil are promising sources of molecules with antioxidant and anti-inflammatory activity. However, their clinical use is limited by issues such as low solubility and poor pharmacokinetic properties. These can be overcome by encapsulating the therapeutic molecules using advanced drug delivery systems such as polymeric nanosystems and nanoemulsions. In this study, agarwood oil nanoemulsion (agarwood-NE) was formulated and tested for its antioxidant and anti-inflammatory potential in cigarette smoke extract (CSE)-treated BCi-NS1.1 airway basal epithelial cells. The findings suggest successful counteractivity of agarwood-NE against CSE-mediated pro-inflammatory effects by reducing the expression of the pro-inflammatory cytokines IL-1α, IL-1β, IL-8, and GDF-15. In addition, agarwood-NE induced the expression of the anti-inflammatory mediators IL-10, IL-18BP, TFF3, GH, VDBP, relaxin-2, IFN-γ, and PDGF. Furthermore, agarwood-NE also induced the expression of antioxidant genes such as GCLC and GSTP1, simultaneously activating the PI3K pro-survival signalling pathway. This study provides proof of the dual anti-inflammatory and antioxidant activity of agarwood-NE, highlighting its enormous potential for COPD treatment.

Cyclooxygenase-2 (COX-2) is a key-type enzyme playing a crucial role in cancer development, making it a target of high interest for drug designers. In the last two decades, numerous selective COX-2 inhibitors have been approved for various clinical conditions. However, data from clinical trials propose that the prolonged use of COX-2 inhibitors is associated with life-threatening cardiovascular side effects. The data indicate that a slight structural modification can help develop COX-2 selective inhibitors with comparative efficacy and limited side effects. In this regard, secondary metabolites from natural sources offer great hope for developing novel COX-2 inhibitors with potential anticancer activity. In recent years, various nature-derived organic scaffolds are being explored as leads for developing new COX-2 inhibitors. The current review attempts to highlight the COX-2 inhibition activity of some naturally occurring secondary metabolites, concerning their capacity to inhibit COX-1 and COX-2 enzymes and inhibit cancer development, aiming to establish a structure-activity relationship.

In this study, natural substances were introduced as primary dental pulp caps for use in pulp therapy, and the antimicrobial and cytotoxic properties of these substances were investigated.

In this in vitro study, the antimicrobial properties of calcium-enriched mixture (CEM) cement, propolis, and propolis individually combined with the extracts of several medicinal plants were investigated against Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Then, the cytotoxicity of each substance or mixture against pulp stem cells extracted from 30 primary healthy teeth was evaluated at 4 concentrations. Data were gathered via observation, and optical density values were obtained using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) test and recorded. SPSS software version 23 was used to analyze the data. Data were evaluated using 2-way analysis of variance and the Tukey test.

Regarding antimicrobial properties, thyme alone and thyme + propolis had the lowest minimum inhibitory concentrations (MICs) against the growth of S. aureus, E. coli, and P. aeruginosa bacteria. For E. faecalis, thyme + propolis had the lowest MIC, followed by thyme alone. At 24 and 72 hours, thyme + propolis, CEM cement, and propolis had the greatest bioviability in the primary dental pulp stem cells, and lavender + propolis had the lowest bioviability.

Of the studied materials, thyme + propolis showed the best results in the measures of practical performance as a dental pulp cap.

Background: Cancer, also known as a malignant tumor, is caused by the activation of oncogenes, which leads to the uncontrolled proliferation of cells that results in swelling. According to the World Health Organization (WHO), cancer is one of the main causes of death worldwide. The main variables limiting the efficacy of anti-tumor treatments are side effects and drug resistance. The search for natural, safe, low toxicity, and efficient chemical compounds in tumor research is essential. Berberine is a pentacyclic isoquinoline quaternary ammonium alkaloid isolated from Berberis and Coptis that has long been used in clinical settings. Studies in recent years have reported the use of berberine in cancer treatment. In this study, we performed a bibliometric analysis of berberine- and tumor-related research. Materials and methods: Relevant articles from January 1, 2002, to December 31, 2021, were identified from the Web of Science Core Collection (WOSCC) of Clarivate Analytics. Microsoft Excel, CiteSpace, VOSviewer, and an online platform were used for the literary metrology analysis. Results: A total of 1368 publications had unique characteristics. Publications from China were the most common (783 articles), and Y. B. Feng (from China) was the most productive author, with the highest total citations. China Medical University (Taiwan) and Sun Yat-sen University (China) were the two organizations with the largest numbers of publications (36 each). Frontiers in Pharmacology was the most commonly occurring journal (29 articles). The present body of research is focused on the mechanism, molecular docking, and oxidative stress of berberine in tumors. Conclusion: Research on berberine and tumors was thoroughly reviewed using knowledge map and bibliometric methods. The results of this study reveal the dynamic evolution of berberine and tumor research and provide a basis for strategic planning in cancer research.

Berberine (BBR), an Eastern traditional medicine, has expressed novel therapeutic activities, especially for chronic diseases like diabetes, hyperlipemia, hypertension, and Alzheimer's disease. However, the low oral bioavailability of BBR has limited the applications of these treatments. Hence, BBRloaded solid lipid nanoparticles (BBR-SLNs) were prepared to improve BBR absorption into systemic circulations via this route.

BBR-loaded solid lipid nanoparticles (BBR-SLNs) were prepared by ultrasonication and then transformed into solid form via spray drying technique. The size morphology of BBR-SLNs was evaluated by dynamic light scattering (DLS) and scanning electron microscope (SEM). Crystallinity of BBR and interaction of BBR with other excipients were checked by spectroscopic methods. Entrapment efficiency of BBR-SLNs as well as BBR release in gastrointestinal conditions were also taken into account. Lastly, SLN's cytotoxicity for loading BBR was determined with human embryonic kidney cells (HEK293).

Stearic acid (SA), glyceryl monostearate (GMS), and poloxamer 407 (P407) were selected for BBRSLNs fabrication. BBR-SLNs had homogenous particle sizes of less than 200 nm, high encapsulation efficiency of nearly 90% and loading capacity of above 12%. BBR-SLN powder could be redispersed without significant changes in physicochemical properties and was stable for 30 days. Spray-dried BBR-SLNs showed a better sustained in vitro release profile than BBR-SLNs suspension and BBR during the initial period, followed by complete dissolution of BBR over 24 hours. Notably, cell viability on HEK293 even increased up to 150% compared to the control sample at 100 μg/mL BBR-unloaded SLNs.

Hence, SLNs may reveal a promising drug delivery system to broaden BBR treatment for oral administration.

Berberine exerts many beneficial effects on lipopolysaccharide (LPS)-induced bovine endometrial epithelial cells (BEECs). Recently, we also found that berberine shows significant antiapoptotic and autophagy-promoting activities, but the underlying mechanism has not been elucidated. This research explored the association between the antiapoptotic and autophagy-promoting activities of berberine in LPS-treated BEECs. BEECs were first preconditioned with an inhibitor of autophagic flux (chloroquine [CQ]) for 1 h, treated with berberine for 2 h, and then incubated with LPS for 3 h. Cell apoptosis was assessed by flow cytometry, and autophagy activities were assessed by immunoblot analysis of LC3II and p62. The results indicated that the antiapoptotic activity of berberine was notably inhibited in LPS-treated BEECs after preconditioning with CQ for 1 h. Furthermore, to determine whether berberine promoted autophagy by activating the nuclear factor-erythroid 2 related factor 2 (Nrf2) signaling pathway, we assessed autophagy in LPS-treated BEECs after preconditioning with a signaling pathway inhibitor of Nrf2 (ML385). The results indicated that the enhanced autophagy activity induced by berberine was partially reversed in LPS-treated BEECs after the Nrf2 signaling pathway was disturbed by ML385. In conclusion, berberine enhances autophagic flux to allow resistance to LPS-induced apoptosis by activating the Nrf2 signaling pathway in BEECs. The present study may provide new insight into the antiapoptotic mechanism of berberine in LPS-induced BEECs.

Influenza pneumonia has challenged public health and social development. One of the hallmarks of severe influenza pneumonia is overproduction of pro-inflammatory cytokines and chemokines, which result from the continuous activation of intracellular signaling pathways, such as the NF-κB pathway, mediated by the interplay between viruses and host pattern recognition receptors (PRRs). It has been reported that traditional Chinese medicines (TCMs) can not only inhibit viral replication and inflammatory responses but also affect the expression of key components of PRRs and NF-κB signaling pathways. However, whether the antiviral and anti-inflammatory roles of TCM are related with its effects on NF-κB signaling pathway activated by PRRs remains unclear. Here, we reviewed the mechanism of PRRs-mediated activation of NF-κB signaling pathway following influenza virus infection and summarized the influence of anti-influenza TCMs on inflammatory responses and the PRRs/NF-κB signaling pathway, so as to provide better understanding of the mode of action of TCMs in the treatment of influenza pneumonia.

The pancreas is a glandular organ with endocrine and exocrine functions necessary for the maintenance of blood glucose homeostasis and secretion of digestive enzymes. Pancreatitis is characterized by inflammation of the pancreas leading to temporary or permanent pancreatic dysfunction. Inflammation and fibrosis caused by chronic pancreatitis exacerbate malignant transformation and significantly increase the risk of developing pancreatic cancer, the world's most aggressive cancer with a 5-year survival rate less than 10%. Berberine (BBR) is a naturally occurring plant-derived polyphenol present in a variety of herbal remedies used in traditional medicine to treat ulcers, infections, jaundice, and inflammation. The current review summarizes the existing in vitro and in vivo evidence on the effects of BBR against pancreatitis and pancreatic cancer with a focus on the signalling mechanisms underlying the effects of BBR.