Scutellaria baicalensis Georgi as a potential therapeutic drug intervention in ulcerative colitis: Mechanisms of action and clinical trials

Table 1 Pharmacological activities of Huangqin and its bioactive components

Ingredients	Pharmacological activities	Experimental type	Specific model	Main findings	Ref.
Huangqin	Anti-inflammatory	In vivo and in vitro	DNP IgE-induced rats and rat, peritoneal mast cells, human mast cells	Suppressing passive cutaneous anaphylactic reactions and reduces histamine release in rat peritoneal mast cells. In human mast cell-1 cells, it restores IL-8 and TNF-α expression while inhibiting MAP kinase expression induced by compound 48/80	[21]
Baicalein		In vivo and in vitro	Mouse macrophage cell line RAW264.7, male Balb/c mice	Inhibiting the increase of RAW264.7 viability. Inhibiting the production of NO through downregulating iNOS without affecting the enzyme activity. Inhibiting intracellular ROS stimulated by LPS, whereas augmented intracellular SOD level in RAW264.7 cells. Inhibiting the production of inflammatory mediators induced by LPS in RAW264.7 cells. Decreasing the level of serum nitrite accumulation and TNF-α	[21,22]
Baicalin		In vitro	HPS SH0165 strain and piglet’s mononuclear phagocytes, high-fat diet-fed rat	Inducing ROS production, arresting the cell cycle and promoting apoptosis via the PKC-MAPK signaling pathway in piglet’s mononuclear phagocytes. Reducing ROS production, suppression of cleavage of caspase-3 in inducing apoptosis, and inhibition of activation of the PKC-MAPK signaling pathway for down-regulating p-JNK, p-p38, p-ERK, p-PKC-α and PKC-δ in PMNP triggered by HPS. Targeting the liver AMPK pathway to benefit obesity-related diseases and hepatic steatosis
Wogonin		In vitro	Mouse macrophage cell line RAW264.7	Restoring the viability of dsRNA (polyinosinic-polycytidylic acid)-induced RAW 264.7 mouse macrophages. Inhibiting the production of oxide, IL-1α, IL-1β, IL-6, IL-10, IP-10, G-CSF, GM-CSF, LIF (IL-6-like cytokine), LIX/CXCL5, MCP-1, M-CSF, MIP-1α, MIP-1β, MIP-2, RANTES/CCL5, TNF-α, and VEGF production. Reducing calcium release and mRNA expression of STAT1 and STAT3 in dsRNA-induced RAW 264.7 cells	[21]
Wogonoside		In vivo	Lipopolysaccharide/D-galactosamine-induced mice	Inhibiting the production of serum alanine transaminase, aspartate aminotransferase, IL-1β, TNF-α, and hepatic malondialdehyde content induced by LPS/GalN. Promoting the expression of Nrf2, NQO-1, GCLC, and HO-1. Reducing expression of hepatic NLRP3, ASC, caspase-1, and IL-1β induced by LPS/GalN	[21]
Oroxylin A		In vivo and in vitro	C57BL/6 mice, BALB/C mice, H460, Jurkat and Lewis cell lines	Inhibiting the generation of Tregs in lung cancer environment by inhibiting the T cells’ response to TGF-β1, decreasing the secretion of TGF-β1 in lung cancer cells via NF-κB signaling	[21]
Baicalein	Regulation of Th1/Th2 balance	In vivo	OVA-induced murine asthma model	Regulating the balance of Th1/Th2 cytokines by suppressing the development of airway inflammation via shifting from a Th2 to Th1 response in the OVA-induced asthma	[23]
Wogonin
Scutellaria baicalensis ethanol extract
Baicalein	Anti-tumor	In vitro and in vivo	Human colorectal cancer HCT116 cells and AOM/DSS-induced ICR mice	Reducing the viability of HCT116 cells. Inducing apoptosis in HCT116 cells. Suppressing the NF-κB activity through the PPARγ activation in HCT116 cells. Suppressing migration in HCT116 cells. Inhibiting AOM/DSS-induced colitis and tumorigenesis	[24]
Wogonin		In vitro and in vivo	A549 cells and A427 cells, human HCC cell line (HepG2), human normal liver cell line (LO2), human hepatocellular carcinoma MHCC97 L and MHCC97 L_luciferase lines, orthotopically HCC-implantation mice model	Inhibiting A549 and A427 lung cancer cell viability without affecting BEAS-2B normal cells. Reducing A427 cell count. Inducing apoptosis of A427 cells. Increasing the expression of caspases 8/9/3 in A427 cells. Inducing ROS generation in A427 cells. Inducing autophagy in A427 cells. Inhibiting cell proliferation and inducing G1 arrest in HCC cells. Inducing cyclin D1 phosphorylation on T286 site and inducing nuclear export in MHCC97 L cells. Promoting G1 arrest of HCC cells through activation of GSK3beta. Suppressing liver tumor growth in vivo	[25,26]
Baicalein	Anti-bacterial	In vitro and in vivo	Escherichia coli cells, clinically isolated and cultured multidrug-resistant strains of Helicobacter pylori, Aeromonas hydrophila and grass carp model	Inhibiting the activity of Escherichia coli. Inhibiting the activity of multidrug-resistant strains of Helicobacter pylori. Inhibiting the activity, biofilm formation and motility of Aeromonas hydrophila	[27-29]
Baicalin
Baicalein	Anti-viral		Network pharmacology	Regulating ACE2 by acting on the RAS pathway. Inhibiting the binding of 2019-nCoV to ACE2 to control the progression of COVID-19	[30]
Wogonin

Th: T helper cell; HCC: Hepatocellular carcinoma; AOM/DSS: Azoxymethane/dextran sodium sulfate; ICR: Institute of cancer research; OVA: Ovalbumin; DNP: Dinitrophenyl; IgE: Immunoglobulin E; IL: Interleukin; TNF-α: Tumor necrosis factor-α; NO: Nitric oxide; iNOS: Inducible nitric oxide synthase; ROS: Reactive oxygen species; LPS: Lipopolysaccharide; SOD: Superoxide Dismutase; PKC-MAPK: Protein kinase C-mitogen-activated protein kinase; p-JNK: Phosphorylated c-Jun N-terminal kinase; p-p38: Phosphorylated p38 mitogen-activated protein kinase; p-ERK: Phosphorylated extracellular signal-regulated kinase; p-PKC-α: Phosphorylated protein kinase C-α; PKC-δ: Protein kinase C-δ; PMNP: Polymorphonuclear leukocyte; HPS: Hemophagocytic syndrome; AMPK: Adenosine monophosphate-activated protein kinase; dsRNA: Double-stranded RNA; G-CSF: Granulocyte colony-stimulating factor; GM-CSF: Granulocyte-macrophage colony-stimulating factor; LIF: Leukemia inhibitory factor; LIX/CXCL5: Lipopolysaccharide-induced CXC chemokine/C-X-C motif chemokine ligand 5; MCP-1: Monocyte chemoattractant protein-1; M-CSF: Macrophage colony-stimulating factor; MIP-1α: Macrophage inflammatory protein-1α; MIP-1β: Macrophage inflammatory protein-1β; MIP-2: Macrophage inflammatory protein-2; RANTES/CCL5: Regulated on activation, normal t cell expressed and secreted/C-C motif chemokine ligand 5; VEGF: Vascular endothelial growth factor; STAT: Signal transducer and activated transcription; GalN: D-Galactosamine; Nrf2: Nuclear factor erythroid 2-related factor 2; NQO-1: Quinone oxidoreductase 1; GCLC: Glutamate-cysteine ligase catalytic subunit; HO-1: Heme oxygenase-1; NLRP3: NOD-like receptor pyrin domain-containing 3; ASC: Apoptosis-associated speck-like protein containing a CARD; TGF-β1: Transforming growth factor-β1; NF-κB: Nuclear factor-κB; PPARγ: Peroxisome proliferator-activated receptor γ; GSK3beta: Glycogen synthase kinase 3β; ACE2: Angiotensin-converting enzyme 2; RAS: Renin-angiotensin system; 2019-nCoV: 2019-novel coronavirus; COVID-19: Coronavirus disease 2019.

Table 2 Clinical trials of Huangqin decoction in ulcerative colitis treatment

Treatments		Dosage of Huangqin	Number of patients in control/intervention	Results (overall response rate), %		Adverse events/number of patients	Ref.
				Control groups	Intervention group
Huangqin decoction	Control group: Oral administration of sulfasalazine 3 g/day. Intervention group: Oral Huangqin decoction (huangqin 20 g, baishao 15 g, gancao 15 g, dazao 30 g). Treatment time: 2 months	20 g	32/32	78.13	81.25	Not reported	[123]
	Control group: Oral sulfasalazine 3 g/day. Intervention group: Oral Huangqin decoction (huangqin 20 g, baishao 15 g, dazao 30 g, gancao 15 g). Treatment time: 2 months	20 g	32/31	87.50	90.32	Not reported	[124]
	Control group: Oral sulfasalazine 9 tablets/day (dose reduced to 4.5 tablets/day after 2 weeks). Intervention group: Oral modified Huangqin decoction (huangqin 8 g, baishao 6 g, zhigancao 4 g, dazao 8 pieces, adjusted according to symptoms). Treatment time: 1 month	8 g	68/68	41.18	97.06	Control group: Leukopenia/3, headache and nausea/3, arthritis/1. Intervention group: 0	[125]
	Control group: Oral sulfasalazine 4 g/d. Intervention group: Oral Huangqin decoction granules (huangqin 20 g, baishao 10 g, gancao 6 g, dazao 10 g). Treatment time: 2 months	20 g	68/68	70	86.7	Not reported	[126]
	Control group: Antibiotics, corticosteroids, immunosuppressants, etc. Intervention group: Oral Huangqin decoction (huangqin 15 g, huanglian 10 g, zhizi 10 g, huangbo 10 g). Treatment time: 30 days	15 g	50/50	68.00	90.00	Not reported	[127]
	Group 1: Oral administration of 4 g/day sulfasalazine + 9 tablets/day berberine. Group 2: Retention enema with Chinese patent medicine named Jiechangning. Group 3: Oral modified Huangqin decoction (huangqin 12 g, shaoyao 9 g, zhigancao 6 g, dazao 10 pieces, adjusted according to symptoms). Group 4: Groups 2 plus 3 regimens. Treatment time: 2 months	12 g	20/20/20/20	Group 1: 65. Group 2: 75. Group 4: 95	70	Not reported	[128]
Huangqin decoction plus western medicine	Control group: Oral mesalazine 4 g/day + peifeikang capsules 1.26 g/day. Intervention group: Oral Peifeikang capsules 1.26 g/day + Huangqin decoction (huangqin 20 g, baishao 15 g, gancao 15 g, dazao 15 g, adjusted according to symptoms). Treatment time: 2 months	20 g	35/35	65.7	85.7	Control group: Mild nausea and vomiting/2. Intervention group: 0	[129]
	Control group: Oral sulfasalazine 4 g/day. Intervention group: Control group treatment + Huangqin decoction granules orally (dazao 10 g, huangqin 2 0 g, gancao 6 g, baishao 10 g). Treatment time: Not stated	20 g	56/56	69.6	92.9	Control group: Arthritis/1, leukopenia/3, headache and nausea/3. Intervention group: 0	[130]
	Control group: Oral mesalazine enteric-coated tablets 3 g/day. Intervention group: Control group treatment + Huangqin decoction granules orally (huangqin 20 g, baishao 10 g, gancao 6 g, dazao 10 g). Treatment time: 2 months	20 g	34/34	76.5	91.2	Not reported	[131]
	Control group: Oral administration of 9 g/day sulfasalazine enteric-coated tablets. Intervention group: Control group treatment + Huangqin decoction orally (huangqin 30 g, baishao 20 g, gancao 20 g, dazao 20 g). Treatment time: 1 month	30 g	37/37	60.53	83.78	Control group: Nausea/4, fatigue/3, dizziness/1. Intervention group: Nausea/1, fatigue/1	[11]
	Control group: Oral mesalazine granules 3 g/day. Intervention group: Control group treatment + Huangqin decoction granules orally (huangqin 20 g, baishao 10 g, gancao 6 g, dazao 10 g). Treatment time: 2 months	20 g	63/63	80.95	96.83	Not reported	[132]
	Control group: Oral mesalazine 3 g/day. Intervention group: Control group treatment + Huangqin decoction orally (huangqin 25 g, baishao 20 g, dazao 30 g, gancao 12 g, adjusted according to symptoms). Treatment time: 3 months	25 g	39/39	58.97	82.05	Control group: Nausea and vomiting/2, fatigue/1, dizziness/3, mild skin itching/2. Intervention group: Nausea and vomiting/1, dizziness/1	[133]
	Control group: Mesalazine sustained-release granules 4 g/day orally. Intervention group: Control group treatment plus modified Huangqin decoction administered orally (huangqin 20 g, baishao 15 g, gancao 15 g, dazao 15 g, adjusted according to symptoms). Treatment time: 2 months	20 g	41/41	68.29	90.24	Not reported	[134]
	Control group: Oral mesalazine granules 4 g/day. Intervention group: Control group treatment + modified Huangqin decoction orally (huangqin 20 g, baishao 15 g, gancao 15 g, dazao 15 g, adjusted according to symptoms). Treatment time: 2 months	20 g	58/58	77.59	91.38	Not reported	[135]
	Control group: Oral mesalazine enteric-coated tablets 1.5 g/day. Intervention group: Control group treatment + Huangqin decoction enema (huangqin 9 g, shaoyao 6 g, dazao 12 g, zhigancao 6 g). Treatment time: 30 days	9 g	40/40	72.50	95.00	Control group: Nausea and vomiting/2, dizziness/1, rash/2. Intervention group: Dizziness/1, rash/1	[136]
	Control group: Oral mesalazine enteric-coated tablets 4 g/day. Intervention group: Control group treatment + Huangqin decoction orally (huangqin 12 g, baishao 15 g, baizhu 15 g, yiyiren 15 g, mudanpi 10 g, diyu 10 g, qinpi 10 g, baiji 6 g, zhigancao 6 g). Treatment time: 2 months	12 g	40/40	75.00	92.50	Not reported	[137]
	Control group: Bifidobacterium quadruple live bacteria tablets 4.5 g + mesalazine enteric-coated tablets 4 g/day orally. Intervention group: Control group treatment + Huangqin decoction enema (dazao 12 pieces, huangqin 9 g, zhigancao 6 g, shaoyao 6 g). Treatment time: 1 month	9 g	47/48	76.60	91.67	Control group: Nausea/1, vomiting/1, abdominal distension/1. Intervention group: Nausea/2, abdominal distension/2	[138]

Table 3 Clinical trials of Gegen Qinlian decoction in ulcerative colitis treatment

Treatments		Dosage of Huangqin	Number of patients in control/intervention	Results (overall response rate), %		Adverse events	Ref.
				Control group	Intervention group
Gegen Qinlian decoction	Control group: Oral administration of 1.5 g/day olsarazine sodium capsules. Intervention group: Modified Gegen Qinlian decoction, oral administration (gegen 15 g, huangqin 15 g, huanglian 15 g, zhigancao 15 g, pugongying 15 g, baijiangcao 30 g, huaihua 15 g, baiji 15 g, wubeizi 30 g, gubaipi 60 g, with modifications according to symptoms). Treatment time: 30 days	15 g	28/32	67.9	90.6	Not reported	[139]
	Control group received enemas combining the following medications: 150 mL saline solution, 0.6 g Xileisan powder, 3.0 g sulfasalazine, 5 mL lidocaine hydrochloride injection, and 0.2 g metronidazole tablets, mixed thoroughly before administration. Intervention group received an additional modified Gegen Qinlian decoction enema (huangqin 30 g, huanglian 30 g, huangbo 30 g, gegen 30 g, yiyiren 30 g, baihuasheshecao 30 g, baijiangcao 20 g, guangmuxiang 20 g, chishao 20 g). Both groups also received oral herbal decoction. Treatment time: 6 weeks	30 g	29/36	55.17	91.67	Control group: Leukopenia/1, mild liver function abnormalities/2. Intervention group: Mild liver function abnormality/1 (mild liver enzymes elevated without a detailed statement)	[140]
	Control group: Oral sulfasalazine 3 g/day. Intervention group: Gegen Qinlian decoction with pugongying enema (pugongying 45 g, gegen 20 g, huangqin 20 g, huanglian 10 g). Treatment time: 45 days	20 g	53/60	75.5	90	Not reported	[141]
	Control group: Oral sulfasalazine tablets 4 g/day + metronidazole 0.4 g enema. Intervention group: Modified Gegen Qinlian decoction orally (gegen 20 g, huangqin 12 g, huanglian 12 g, baitouweng 12 g, fuling 10 g, cheqianzi 10 g, dangshen 10 g, muxiang 10 g, jineijin 10 g, shanzha 10 g, wumei 6 g, shiliupi 6 g, and zhigancao 6 g, adjusted according to symptoms). Treatment time: 2 months	12 g	89/89	80.9	92.14	Control group: Facial flushing with headache/2. Intervention group: 0	[142]
	Control group: Mesalazine suppositories rectally twice daily. Intervention group: Modified Gegen Qinlian decoction enema (gegen 30 g, huanglian 15 g, huangqin 20 g, baijiangcao 15 g, machixian 15 g, xianhecao 15 g, baishao 15 g, huangqi 30 g, dangshen 10 g, zhigancao 5 g). Treatment time: 2 months	20 g	40/42	80.0	95.2	Control group: Gastrointestinal reactions (nausea, vomiting, etc.)/3, mild headache/1. Intervention group: 0	[143]
	Control group: Oral administration of 3-4 g/day of sulfasalazine enteric-coated tablets. Intervention group: Modified Gegen Qinlian decoction enema (gegen 20 g, huanglian 9 g, huangqin 10 g, pugongying 30 g, yiyiren 60 g, baiji 20 g, diyu 15 g, huaihua 10 g, gancao 5 g, adjusted according to symptoms). Treatment time: 30 days	10 g	60/60	71.7	86.7	Not reported	[144]
Gegen Qinlian decoction plus western medicine	Control group: 0.5% metronidazole 100 mL + sulfasalazine 2.5 g enema. Intervention group: Sulfasalazine 2.5 g + modified Gegen Qinlian decoction enema (gegen 20 g, huangqin 25 g, huanglian 25 g, baiji 30 g, baizhu 18 g, baishao 18 g). Treatment time: 30 days	25 g	23/23	60.9	91.3	Control group: Gastrointestinal discomfort including nausea, vomiting, loss of appetite, and abdominal distension/7, mild dizziness/1. Intervention group: 0	[145]
	Control group: Oral sulfasalazine 1 g/day + sodium succinate hydrocortisone 100 mg enema. Intervention group: Control group therapy + modified Gegen Qinlian decoction orally (gegen 30 g, huangqin 15 g, dangshen 12 g, baizhu 12 g, fuling 30 g, yiyiren 30 g, muxiang 9 g, huoxiang 9 g, huanglian 12 g, dongguaren 30 g, gancao 6 g; adjusted according to symptoms). Treatment time: 1-2 weeks	15 g	45/45	76.56	91.11	Not reported	[146]
	Control group: 3 capsules/d of Baluosulindipine sodium capsules via enema + 4 g/day of sulfasalazine enteric-coated tablets orally. Intervention group: Sulfasalazine enteric-coated tablets 4 g/day orally + Gegen Qinlian decoction enema (gegen 20 g, huangqin 25 g, huanglian 25 g, baiji 30 g, baizhu 18 g, baishao 18 g, danggui 15 g). Treatment time: 1 month	25 g	30/32	73.33	93.75	Not reported	[147]
	Control group: Oral mesalazine 1.5 g/day. Intervention group: Control group treatment + oral administration of Gegen Qinlian decoction (gegen 15 g, huangqin 9 g, huanglian 9 g, gancao 6 g). Treatment time: Control group, more than 2 weeks. Intervention group: 21 days	9 g	45/45	84.4	97.7	Not reported	[148]
	Control group: Bacillus subtilis dual-strain live bacteria capsules 0.75 g/day orally. Intervention group: Control group treatment + Gegen Qinlian decoction enema (baishao 18 g, baizhu 18 g, baiji 30 g, huanglian 25 g, huangqin 25 g, gegen 20 g). Treatment time: 30 days	25 g	39/40	76.92	92.50	Control group: Gastrointestinal discomfort/2. Intervention group: Mild dizziness/1	[149]
	Control group: Oral sulfasalazine 4 g/day. Intervention group: Control group treatment + oral administration of Gegen Qinlian decoction (gegen 30 g, huanglian 12 g, huangqin 15 g, fuling 30 g, baizhu 12 g, muxiang 9 g, dongguaren 30 g, dangshen 12 g, huoxiang 9 g, yiyiren 30 g, gancao 6 g, adjusted according to symptoms). Treatment time: 1 month	15 g	30/30	76.67	93.33	Control group: Rash/1, leukopenia/1, elevated transaminases/1; intervention group: Fatigue/1, rash/1	[150]
	Control group: Oral administration of 4 g/day sulfasalazine enteric-coated tablets. Intervention group: Control group therapy + Gegen Qinlian decoction enema (huanglian 23 g, baizhu 20 g, baishaot 15 g, huangqin 24 g, gegen 17 g, danggui 13 g, baiji 29 g). Treatment time: 1 month	24 g	48/48	83.3	95.9	Not reported	[151]
	Control group: Bacillus subtilis and Bacillus licheniformis dual-strain live bacteria capsules 1.5 g/day orally. Intervention group: Control group treatment + Gegen Qinlian decoction enema (gancao 10 g, huangqin 15 g, huanglian 10 g, gegen 30 g). Treatment time: 1 month	15 g	16/24	75.0	91.7	Not reported	[152]
	Control group: Oral mesalazine enteric-coated tablets 1.5 g/day + hydrocortisone succinate sodium 100 mg enema twice daily. Intervention group: Control group treatment + modified Gegen Qinlian decoction orally (gegen 15 g, baitouweng 15 g, dangshen 15 g, baizhu 15 g, fuling 12 g, yiyiren 12 g, huanglian 9 g, huangqin 9 g, huangbo 9 g, shanyao 12 g, danggui 12 g, muxiang 9 g, yanhusuo 9 g, baiji 9 g, sanqi 9 g, gancao 6 g). Treatment time: 1 month	9 g	41/41	80.49	95.12	Control group: Dizziness and headache/3, nausea and vomiting/3, abdominal distension/1, generalised fatigue/2; intervention group: Nausea and vomiting/1, abdominal distension/1	[153]
	Control group: Mesalazine enteric-coated tablets 3 g/day orally. Intervention group: Control group treatment + modified Gegen Qinlian decoction administered orally (huanglian 3 g, huangqin 10 g, gegen 15 g, machixian 15 g, yiyiren 15 g, shaoyao 10 g, baijiangcao 15 g, hongteng 15 g, fried muxiang 10 g, zhigancao10 g, adjusted according to symptoms). Treatment time: 3 months	10 g	30/30	70.00	93.33	Control group: 0. Intervention group: Gastric discomfort/1	[154]
	Control group: Oral mesalazine enteric-coated tablets 3 g/day. Intervention group: Control group treatment + modified Gegen Qinlian decoction orally (gegen 15 g, huangqin 15 g, huanglian 5 g, gancao 6 g, zhike 15 g, baizhu 15 g, fuling 10 g). Treatment time: 2 months	15 g	40/40	72.5	92.5	Not reported	[155]
	Control group: Oral mesalazine enteric-coated tablets 3 g/day. Intervention group: Control group treatment + modified Gegen Qinlian decoction orally (yiyiren 30 g, machixian 20 g, chishizhi 20 g, fuling 20 g, gegen, baizhu 15 g, dangshen 15 g, baishao 15 g, muxiang 10 g, chenpi 10 g, huanglian 9 g, huangqin 9 g, gancao 5 g). Treatment time: 1 month	9 g	30/30	80.00	93.33	Not reported	[156]
	Control group: Oral mesalazine enteric-coated tablets 1.5 g/day + hydrocortisone succinate sodium 100 mL enema twice daily. Intervention group: Control group treatment + modified Gegen Qinlian decoction orally (gegen 15 g, baitouweng 15 g, dangshen 15 g, fried baizhu 15 g, yiyiren 12 g, danggui 12 g, shanyao 12 g, fuling 12 g, huanglian 9 g, huangbo 9 g, baiji 9 g, yanhusuo 9 g, sanqi 9 g, muxiang 9 g, huangqin 9 g, gancao 6 g). Treatment time: 1 month	9 g	32/32	84.38	96.88	Not reported	[157]
	Control group: Oral mesalazine sustained-release granules 4 g/day. Intervention group: Control group treatment + modified Gegen Qinlian decoction orally (gegen 15 g, baitouweng 15 g, huangqin 9 g, huanglian 9 g, diyu 9 g, huaihua 9 g, gancao 6 g). Treatment time: 28 days	9 g	31/31	80.65	96.77	Control group: Intestinal obstruction/3, acute intestinal perforation/1, major intestinal hemorrhage/2. Intervention group: Intestinal obstruction/1	[158]
	Control group: Oral mesalazine enteric-coated tablets 1 g/day + sodium hydrocortisone succinate 50 mg enema twice daily. Intervention group: Control group therapy + modified Gegen Qinlian decoction orally (gegen 5 g, baizhu 5 g, dangshen 5 g, baitouweng 15 g, shanyao 12 g, yiyiren 12 g, fuling 12 g, danggui 12 g, huangbo 9 g, huanglian 9 g, huangqin 9 g, sanqi 9 g, yanhusuo 9 g, muxiang 9 g, baiji 9 g, gancao 6 g). Treatment time: 1 month	9 g	51/51	76.47	92.16	Not reported	[159]
	Control group: Oral mesalazine enteric-coated tablets 3 g/day. Intervention group: Control group treatment + Gegen Qinlian decoction enema (gegen 30 g, huanglian 10 g, gancao 6 g, huangqin 10 g). Treatment time: 2 months	10 g	46/48	73.91	91.67	Not reported	[160]
	Control group: Oral mesalazine enteric-coated tablets 1.5 g/day. Intervention group: Control group treatment + modified Gegen Qinlian decoction orally (gegen 15 g, huanglian 9 g, huangqin 9 g, gancao 6 g, adjusted according to symptoms). Treatment time: 1 month	9 g	50/50	80.00	94.00	Control group: Abdominal distension/2, indigestion/1, dizziness and headache/2, fatigue/1, rash/1. Intervention group: Abdominal distension/1, indigestion/2, dizziness and headache/1, fatigue/1	[161]
	Control group: Oral mesalazine enteric-coated tablets (4 g/day during acute phase, 1.5 g/day during maintenance phase). Intervention group: Control group treatment + oral administration of Gegen Qinlian decoction (gegen 15 g, huanglian 9 g, huangqin 9 g, gancao 6 g, adjusted according to symptoms). Treatment time: 2 months	9 g	39/39	82.05	97.43	Not reported	[162]

Table 4 Clinical trials of other Huangqin-based traditional Chinese medicine formula in ulcerative colitis treatment

Treatments		Dosage of Huangqin	Number of patients	Results (overall response rate), %		Adverse events	Ref.
				Control group	Intervention group
Other Huangqin-based formula	Control group: Mesalazine enteric-coated tablets 3 g/day orally. Intervention group: Oral administration of Qinlian Lizhong decoction (huangqin 12 g, huanglian 9 g, baishao 15 g, dangshen 9 g, ganjiang 6 g, baizhu 12 g, xianhecao 15 g, shiliupi 12 g, with adjustments according to symptoms). Treatment time: 2 months	12 g	37/38	67.6	81.6	Not reported	[163]
	Control group: Mesalazine enteric-coated tablets 3 g/day orally. Intervention group: Oral administration of Qinlian Lizhong decoction (huangqin 12 g, huanglian 9 g, baishao 15 g, dangshen 9 g, ganjiang 6 g, baizhu 12 g, xianhecao 15 g, shiliupi 12 g, with adjustments according to symptoms). Treatment time: 2 months	12 g	57/58	70.17	84.48	Control group: Mild nausea and dizziness/1. Intervention group: 0	[164]
Other Huangqin-based formula plus western medicine	Control group: Oral mesalazine enteric-coated tablets 4 g/day. Intervention group: Control group treatment + compound Qinbai granules 12 g enema (in-house preparation). Treatment time: 2 months	Unknown	60/60	78.33	95.00	Not reported	[165]
	Control group: Oral mesalazine sustained-release granules 1.5 g/day. Intervention group: Control group treatment + 10 mg Qinbai granules enema (in-house preparation). Treatment time: 3 months	Unknown	36/37	72.2	91.9	Not reported	[166]
	Control group: Oral mesalazine sustained-release tablets 0.3 g/day. Intervention group: Control group treatment + Huangqin Shaoyao decoction orally (huangqi 30 g, huangqin 20 g, dangshen 20 g, shaoyao 15 g, jinyinhua 15 g, dazao 15 g, gancao 10 g, baizhu 9 g, danggui 9 g, huanglian 6 g, muxiang 6 g, adjusted according to symptoms). Treatment time: 12 weeks	20 g	49/49	77.55	91.84	Control group: Nausea and vomiting/1, abdominal distension/2, headache and fatigue/1. Intervention group: Nausea and vomiting/2, abdominal distension/1	[167]