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.