Baicalin

Baicalin is a flavonoid glycoside isolated from Scutellaria baicalensis. Baicalin reduces the expression of NF-κB.

In Vitro:Baicalin protects against ischemia-reperfusion injury (IRI) by altering the production of various mediators, including reactive oxygen species (ROS), Toll-like receptor (TLR)2 and TLR4, NF-κB, Bax, and Bcl-2. Baicalin treatment inhibits the increased expression of the proinflammatory cytokines TLR2/4, MyD88, p-NF-κB, and p- IκB, as well as increase the expression of IκB protein, an NF-κB inhibitor, with the degree of inhibition positively related to the dosage of Baicalin[1]. Cell viability is determined by MTT assay. Compared with control cells, cell viability is significantly decreased in SH-SY5Y cells treated with thrombin. Pre-treatment with Baicalin (5, 10, 20 μM) increases cell viability in a dose-dependent manner compared with cells treated thrombin alone[2].

In Vivo:Baicalin pretreatment dose-dependently protects against a loss of renal function, with the two higher doses (10 and 100 mg/kg) significantly decreasing Scr and blood urea nitrogen (BUN) concentrations. Tissue injury, as assessed using a 0-3 point scoring system, is lower for the Baicalin treated groups than for the ischemia-reperfusion (IR)+saline group. Compared with the sham group, malondialdehyde (MDA) content is only slightly up-regulated and the SOD activity is only slightly down-regulated in rats treated with 10 and 100 mg/kg Baicalin, indicating that Baicalin abrogates the increase in oxidative stress following reperfusion[1].

References:
[1]. Lin M, et al. The protective effect of Baicalin against renal ischemia-reperfusion injury through inhibition of inflammation and apoptosis. BMC Complement Altern Med. 2014 Jan 13;14:19. [2]. Ju XN, et al. Baicalin protects against thrombin induced cell injury in SH-SY5Y cells. Int J Clin Exp Pathol. 2015 Nov 1;8(11):14021-7.

Baicalin induces apoptosis via mitochondrial pathway as prooxidant.[Pubmed:11841838]

Mol Immunol. 2002 Feb;38(10):781-91.

Baicalin is a flavonoid and a major component of a herbal medicine, Sho-saiko-to, which is commonly used for treatment of chronic hepatitis in Japan and China. Flavonoids including Baicalin have been reported to not only function as anti-oxidants but also cause cytotoxic effect. We investigated the mechanism of Baicalin-induced cytotoxicity in leukemia-derived T cell line, Jurkat cells. When cells were cultured with 50-200 microg/ml Baicalin for 6h, caspase-3 was activated and then cells fell into apoptosis. Induction of apoptosis by Baicalin was accompanied with the marginal generation of intracellular reactive oxygen species (ROS), the increase of the cytosolic fractions of cytochrome c, and the disruption of mitochondrial transmembrane potential (DeltaPsi(m)) prior to the activation of caspase-3. The pre-culture with 5 mM of buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, facilitated Baicalin-induced disruption of DeltaPsi(m) and induction of apoptosis. The pre-culture with N-benzyloxycarbonyl-valyl-alanyl-aspartyl fluoromethylketone (Z-VAD-fmk), a pan-caspase inhibitor, partially suppressed the induction of apoptosis. On the other hand, Baicalin showed little toxic effect on peripheral blood mononuclear cells (PBMCs) from healthy volunteers. These results indicate that Baicalin acts as a prooxidant and induces caspase-3 activation and apoptosis via mitochondrial pathway.

Baicalin, baicalein and wogonin inhibits high glucose-induced vascular inflammation in vitro and in vivo.[Pubmed:25739393]

BMB Rep. 2015 Sep;48(9):519-24.

Vascular inflammatory process has been suggested to play a key role in initiation and progression of atherosclerosis, a major complication of diabetes mellitus. Thus, in this study, we attempted to determine whether three structurally related polyphenols found in the Chinese herb Huang Qui, namely Baicalin, baicalein, and wogonin, can suppress vascular inflammatory processes induced by high glucose (HG) in human umbilical vein endothelial cells (HUVECs) and mice. Data showed that HG induced markedly increased vascular permeability, monocyte adhesion, expressions of cell adhesion molecules (CAMs), formation of reactive oxygen species (ROS) and activation of nuclear factor (NF)-kappaB. Remarkably, all of the above mentioned vascular inflammatory effects of HG were attenuated by pretreatment with Baicalin, baicalein, and wogonin. Vascular inflammatory responses induced by HG are critical events underlying development of various diabetic complications, therefore, our results suggest that Baicalin, baicalein, and wogonin may have significant therapeutic benefits against diabetic complications and atherosclerosis.

Baicalin attenuates global cerebral ischemia/reperfusion injury in gerbils via anti-oxidative and anti-apoptotic pathways.[Pubmed:21600966]

Brain Res Bull. 2011 Jul 15;85(6):396-402.

Baicalin is an important medicinal herb purified from the dry roots of Scutellaria baicalensis Georgi. The present study was undertaken to evaluate the neuroprotective effects of Baicalin in gerbils subjected to transient global cerebral ischemic-reperfusion injury. Baicalin at doses of 50, 100 and 200mg/kg was intraperitoneally injected into the gerbils immediately after cerebral ischemia. Seven days after reperfusion, hematoxylin and eosin (HE) staining was performed to analyze hippocampal CA1 pyramidal damage histopathologically. In addition, in order to understand the potential protective mechanism of Baicalin, we examined anti-oxidative enzymes, such superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), non-enzymatic scavenger glutathione (GSH) and measured the content of malondialdehyde (MDA) in hippocampus. The mRNA and protein expressions of BDNF were determined in ischemic hippocampus by real-time RT-PCR and Western blot, respectively. Evidence for neuronal apoptosis was detected by real-time RT-PCR, Western blot and caspase-3 activity measurement. Histopathological examination showed that the administration of Baicalin by the dose of 100 and 200mg/kg significantly attenuated ischemia-induced neuronal cell damage. Reduced level of MDA, obviously elevated activities of SOD and GSH as well as GSH-PX were also found in Baicalin-treated groups. Further investigation demonstrated that treatment with Baicalin remarkably promoted the expression of BDNF and inhibited the expression of caspase-3 at mRNA and protein levels by real-time RT-PCR and Western blot, respectively. Besides, caspase-3 activity assay also elucidated that the administration of Baicalin could significantly suppress caspase-3 in ischemic gerbils hippocampus. Theses findings suggest that Baicalin's neuroprotection appears to be associated with its anti-oxidative and anti-apoptotic properties in global cerebral ischemia in the gerbils.

Baicalin Inhibits Lipopolysaccharide-Induced Inflammation Through Signaling NF-kappaB Pathway in HBE16 Airway Epithelial Cells.[Pubmed:25630720]

Inflammation. 2015 Aug;38(4):1493-501.

Baicalin, a flavonoid monomer derived from Scutellaria baicalensis called Huangqin in mandarin, is the main active ingredient contributing to S. baicalensis' efficacy. It is known in China that Baicalin has potential therapeutic effects on inflammatory diseases. However, its anti-inflammatory mechanism has still not been fully interpreted. We aim to investigate the anti-inflammatory effect of Baicalin on lipopolysaccharide (LPS)-induced inflammation in HBE16 airway epithelial cells and also to explore the underlying signaling mechanisms. The anti-inflammatory action of Baicalin was evaluated in human airway epithelial cells HBE16 treated with LPS. Airway epithelial cells HBE16 were pretreated with a range of concentrations of Baicalin for 30 min and then stimulated with 10 mug/ml LPS. The secretions of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha) in cell culture supernatants were quantified by enzyme-linked immunosorbent assay (ELISA). The messenger RNA (mRNA) expressions of IL-6, IL-8, and TNF-alpha were tested by quantitative real-time polymerase chain reaction (real-time RT-PCR). Furthermore, Western blotting was used to determine whether the signaling pathway NF-kappaB was involved in the anti-inflammatory action of Baicalin. The inflammatory cell model was successfully built with 10 mug/ml LPS for 24 h in our in vitro experiments. Both the secretions and the mRNA expressions of IL-6, IL-8, and TNF-alpha were significantly inhibited by Baicalin. Moreover, the expression levels of phospho-IKKalpha/beta and phospho-NF-kappaB p65 were downregulated, and the phospho-IkappaB-alpha level was upregulated by Baicalin. These findings suggest that the anti-inflammatory properties of Baicalin may be resulted from the inhibition of IL-6, IL-8, and TNF-alpha expression via preventing signaling NF-kappaB pathway in HBE16 airway epithelial cells. In addition, this study provides evidence to understand the therapeutic effects of Baicalin on inflammatory diseases in clinical practice.