Therapeutic Effects Of Baicalin Research Articles

Baicalin induces ferroptosis in oral squamous cell carcinoma by suppressing the activity of FTH1.

This study investigated the role of the ferroptosis-related gene FTH1 in oral squamous cell carcinoma (OSCC) and evaluated the therapeutic potential of baicalin in OSCC cell treatment. A prognostic model was established by bioinformatic analysis, consisting of 12 ferroptosis related genes (FRGs), and FTH1 was selected as the most significantly up-regulated FRGs. The clinical correlation of FTH1 in OSCC samples was evaluated by both immunohistochemical and bioinformatic characterizations. The effects of FTH1 on migration, invasion, epithelial-mesenchymal transition (EMT) and proliferation were determined by wound healing assays, transwell assays, western blotting and 5'-ethynl 2'-deoxyuridine proliferation assays, respectively. The effects of FTH1 on ferroptosis were tested via ferroptosis markers and Mito Tracker staining. In addition, the therapeutic effects of baicalin on OSCC cells were confirmed using EMT, migration, invasion, proliferation and ferroptosis assays. The 12 FRGs werepredictive of theprognosis for OSCC patients, and FTH1 expression was identified as significantly up-regulated in OSCC samples, which was highly associated with survival, immune cell infiltration and drug sensitivity. Moreover, knocking down FTH1 inhibited cell proliferation, EMT and invasive phenotypes, but induced ferroptosis in OSCC cells (Cal27 and SCC25). Furthermore, baicalin directly suppressed expression of FTH1 in OSCC cells, and effectively promoted ferroptosis and inhibited the proliferation as well as EMT by directly targeting FTH1. This study has demonstrated that FTH1 is a therapeutic target for OSCC treatment, and has provided evidence that baicalin offers a promising alternative for OSCC treatment.

Therapeutic Effects of Baicalin on Diseases Related to Gut-Brain Axis Dysfunctions.

The gut-brain axis is an active area of research. Several representative diseases, including central nervous system disorders (Alzheimer's disease, Parkinson's disease, and depression), metabolic disorders (obesity-related diseases), and intestinal disorders (inflammatory bowel disease and dysbiosis), are associated with the dysfunctional gut-brain axis. Baicalin, a bioactive flavonoid extracted from Scutellaria baicalensis, is reported to exert various pharmacological effects. This narrative review summarizes the molecular mechanisms and potential targets of baicalin in disorders of the gut-brain axis. Baicalin protects the central nervous system through anti-neuroinflammatory and anti-neuronal apoptotic effects, suppresses obesity through anti-inflammatory and antioxidant effects, and alleviates intestinal disorders through regulatory effects on intestinal microorganisms and short-chain fatty acid production. The bioactivities of baicalin are mediated through the gut-brain axis. This review comprehensively summarizes the regulatory role of baicalin in gut-brain axis disorders, laying a foundation for future research, although further confirmatory basic research is required.

Baicalin ameliorates multidrug-resistant Pseudomonas aeruginosa induced pulmonary inflammation in rat via arginine biosynthesis

Multidrug-resistance (MDR) Pseudomonas aeruginosa (P. aeruginosa) is a lethal gram-negative pathogen causing hospital-acquired and ventilator-associated pneumonia, which is difficult to treat. Our previous studies confirmed that baicalin, an essential bioactive component in Scutellaria baicalensis Georgi, exhibited anti-inflammatory effects in an acute pneumonia rat model induced by MDR P. aeruginosa. However, this effect of baicalin in constrast its low bioavailability, and its mechanism of action is still unknown. Thus, this study investigated whether the therapeutic effects of baicalin against MDR P. aeruginosa acute pneumonia are owing to the regulation of gut microbiota and their metabolites using pyrosequencing of the 16S rRNA genes in rat feces and metabolomics. As a result, baicalin attenuated the inflammation by acting directly on neutrophils and regulated the production of the inflammatory cytokines TNF-α, IL-1β, IL-6, and IL-10. The mechanisms were through down-regulation of TLR4 and inhibition of NF-κB. Furthermore, pyrosequencing of the 16S rRNA genes in rat feces revealed that baicalin regulated the composition of gut microbial communities. At the genus level, baicalin efficiently increased the abundance of Ligilactobacillus, Lactobacillus and Bacteroides, but decreased the abundance of Muribaculaceae and Alistipes. Further, arginine biosynthesis was analyzed as the core pathway regulated by baicalin via combination with predicting gut microbiota function and targeted metabolomics. In conclusion, this study has demonstrated that baicalin relieved inflammatory injury in acute pneumonia rat induced by MDR P. aeruginosa via arginine biosynthesis associated with gut microbiota. Baicalin could be a promising and effective adjunctive therapy for lung inflammation caused by MDR P. aeruginosa infection.

Baicalin Exerts a Protective Effect in Diabetic Nephropathy by Repressing Inflammation and Oxidative Stress Through the SphK1/S1P/NF-κB Signaling Pathway.

Inflammation and oxidative stress contribute to the development of diabetic nephropathy (DN). Baicalin (BA) shows renal protection against DN through its anti-inflammatory and anti-oxidant properties. However, the molecular mechanism by which BA exerts the therapeutic effects on DN remains to be investigated. The db/db mice and high glucose (HG)-induced HK-2 cells were used as the in vivo and in vitro model of DN, respectively. The effects of BA were assessed by detecting the related blood and urine biochemical parameters, kidney histopathology, inflammatory cytokine production, oxidative stress indicators, and apoptosis. Cell viability and apoptosis were detected by CCK-8 assay and TUNEL assay, respectively. Related protein levels were measured by an immunoblotting method. In db/db model mice, BA reduced serum glucose concentration, decreased blood lipid levels, ameliorated kidney functions, and decreased histopathological changes in kidney tissues. BA also alleviated oxidative stress and inflammation in db/db mice. In addition, BA blocked the activation of sphingosine kinases type 1/sphingosine 1-phosphate (SphK1/S1P)/NF-κB pathway in db/db mice. In HK-2 cells, BA hindered HG-induced apoptosis, oxidative stress and inflammation, while overexpression of SphK1 or S1P could reverse these effects. BA alleviated HG-induced apoptosis, oxidative stress and inflammation in HK-2 cells through the S1P/NF-κB pathway. Furthermore, BA blocked the NF-κB signaling by diminishing p65 nuclear translocation via the SphK1/S1P pathway. Our study strongly suggests that BA protects against DN via ameliorating inflammation, oxidative stress and apoptosis through the SphK1/S1P/NF-κB pathway. This study provides a novel insight into the therapeutic effects of BA in DN.

Scutellaria baicalensis and its constituents baicalin and baicalein as antidotes or protective agents against chemical toxicities: a comprehensive review.

Scutellaria baicalensis (SB), also known as the Chinese skullcap, has a long history of being used in Chinese medicine to treat a variety of conditions ranging from microbial infections to metabolic syndrome and malignancies. Numerous studies have reported that treatment with total SB extract or two main flavonoids found in its root and leaves, baicalin (BA) and baicalein (BE), can prevent or alleviate the detrimental toxic effects of exposure to various chemical compounds. It has been shown that BA and BE are generally behind the protective effects of SB against toxicants. This paper aimed to review the protective and therapeutic effects of SB and its main components BA and BE against chemical compounds that can cause intoxication after acute or chronic exposure and seriously affect different vital organs including the brain, heart, liver, and kidneys. In this review paper, we had a look into a total of 221 in vitro and in vivo studies from 1995 to 2021 from the scientific databases PubMed, Scopus, and Web of Science which reported protective or therapeutic effects of BA, BE, or SB against drugs and chemicals that one might be exposed to on a professional or accidental basis and compounds that are primarily used to simulate disease models. In conclusion, the protective effects of SB and its flavonoids can be mainly attributed to increase in antioxidants enzymes, inhibition of lipid peroxidation, reduction of inflammatory cytokines, and suppression of apoptosis pathway.

Baicalin alleviates collagen‑induced arthritis and suppresses TLR2/MYD88/NF‑κB p65 signaling in rats and HFLS‑RAs.

Baicalin is a flavonoid isolated from the root of Scutellaria baicalensis with anti-inflammatory, antioxidant and antiapoptotic pharmacological properties. However, the therapeutic effect of baicalin on rheumatoid arthritis (RA) is not completely understood. The present study aimed to explore the therapeutic potential and mechanisms underlying baicalin in collagen-induced arthritis (CIA) model rats. CIA was induced in male SD rats. The hind paw thickness and severity of joint injury were monitored to assess the onset of arthritis. At 28 days after the initial immunization, different doses of baicalin were administered once daily via oral gavage for 40 days. The radiologic and pathological alterations were examined using X-ray, and hematoxylin and eosin staining, respectively. ELISA was employed to measure the serum levels of proinflammatory cytokines. Reverse transcription-quantitative PCR and western blotting were conducted to determine the expression of toll-like receptor (TLR)2, myeloid differentiation factor 88 (MYD88) and NF-κB p65. Baicalin treatment noticeably alleviated radiographic and histologic abnormalities in the hind paw joints of CIA model rats in a dose-dependent manner. The serum levels of proinflammatory cytokines were significantly decreased in baicalin-treated CIA model rats compared with vehicle-treated CIA model rats. The mRNA expression levels of TLR2 and MYD88, as well as the protein expression levels of TLR2, MYD88 and NF-κB p65 were significantly decreased by baicalin treatment in the synovial tissue of CIA model rats and human RA fibroblast-like synoviocytes. The results suggested that baicalin may exert a beneficial effect on CIA, which may be mediated by inhibiting the TLR2/MYD88/NF-κB signaling pathway.

The Comparative Study of the Therapeutic Effects and Mechanism of Baicalin, Baicalein, and Their Combination on Ulcerative Colitis Rat.

Introduction: Ulcerative colitis (UC) is an inflammatory bowel disease with a high incidence rate and a difficult treatment regimen. Recently, significant advances in the treatment of intestinal diseases, particularly UC, have been made with the use of the drugs baicalin and baicalein, separately or in combination. However, the therapeutic efficacy and mechanism of action of baicalin, baicalein, and their combination therapy, in the treatment of UC has not been fully elucidated. Materials and Methods: we constructed a UC rat model that encompassed a variety of complex factors, including a high-sugar and high-fat diet, a high temperature and humidity environment (HTHE), excess drinking, and infection of Escherichia coli. Model rats were then treated with baicalin, baicalein, or a combination of the two. Results: The results showed significant differences in the therapeutic effects of baicalin, baicalein, and the combination therapy, in the treatment of UC, as well as differences in the inhibition of inflammation via the nuclear factor-κB and MAPK pathways. The rat model of UC was established as described above. Then, the rats were treated for 7 days with baicalin (100 mg kg-1), baicalein (100 mg kg-1), or both (100 mg kg-1, baicalin: baicalein = 4:1/1:1). Clinical symptoms and signs, body temperature, organ indices, histopathology, blood biochemistry, and metabolites were examined to compare treatment effects and indicators of UC. Baicalin, YSR (Young Scutellaria baicalensis ratio of baicalin and baicalein), baicalein, and WSR (Withered Scutellaria baicalensis ratio of baicalin and baicalein) had significantly different effects in terms of clinical symptoms and signs, body temperature, organ indices, serum inflammatory cytokine levels, blood biochemistry, and histopathology changes in the main organs; YSR exhibited the best treatment effects. LC-MS/MS was used to detect the conversion of baicalin, baicalein, or both, into the six types of metabolites: baicalin, wogonoside, oroxin A, baicalein, wogonin, and oroxylin A. The levels of the six metabolites under the different treatment conditions were significantly different in the large intestine, small intestine, and lungs, but not in the blood. The levels of the six metabolites were significantly different in the large intestine, small intestine, and lung, but not in the serum. Conclusion: All these results indicate that baicalin and baicalein should be used more accurately in specific diseases, especially baicalin or high content of baicalin in Scutellaria baicalensis (Tiaoqin) should be preferred in treatment of UC.

The Therapeutic Effects of Baicalin on Vitiligo Mice.

Vitiligo is a commom disease of skin. Its pathogenesis is complex, resulting in the incapacity to find a targeted cure. Baicalin, which is isolated from Scutellariae radix, has been known to exhibit a number of pharmacological effects on autoimmune diseases. In this study, we explored the effects of Baicalin on the recovery of vitiligo stimulated by monophenylketone in mice. We observed that Baicalin slowed down the progression of depigmentation, decreased the incidence of depigmentation, and reduced the area of depigmentation. Moreover, reflectance confocal microscopy (RCM) shown that Baicalin increased the epidermal melanocytes in depigmented skin. Baicalin decreased CD8 + T cell infiltration in mice skin, and decreased the expression of CXCL10 and CXCR3. Baicalin significantly decreased the levels of serum cytokine (interleukin [IL]-6, tumor necrosis factor [TNF]-α, interferon-γ [IFN-γ], and IL-13). Collectively, these data suggest that Baicalin play an important role in the occurrence and development of vitiligo.

Therapeutic effects of baicalin on lupus nephritis in a lupus-prone mouse model and its regulatory role in follicular helper T cell differentiation

Objective To evaluate the therapeutic effect of baicalin on lupus nephritis in a lupus-prone mouse model, and to investigate its regulatory role in the differentiation of follicular helper T (Tfh) cells. Methods Eight 12-week-old female MRL/lpr lupus-prone mice were randomly and equally divided into two groups by a random number table i.e., baicalin group and control group intraperitoneally injected with 200 mg/kg baicalin sodium and chloride physiological solution, respectively, once every day for 4 weeks. After the end of treatment, Coomassie brilliant blue staining was performed to detect the level of 24-hour urine protein. Then, the mice were sacrificed, and the spleens were resected and weighed. Mononuclear cells were isolated from these spleens, and flow cytometry was conducted to determine the proportion of Tfh cells. Additionally, the kidneys were resected and subjected to hematoxylin and eosin (HE) staining for the evaluation of kidney impairment. Moreover, some other mononuclear cells were isolated from the spleens of the lupus-prone mice in the control group, and magnetic activated cell sorting (MACS) was performed to isolate naive CD4+ T cells, which were divided into 3 groups: blank control group receiving no treatment, induction group treated with 10 μg/L anti-interleukin (IL) -21 and anti-IL-6 antibodies and 3 μg/L anti-CD3 and anti-CD28 antibodies for 5 days, and intervention group additionally treated with 40 μmol/L baicalin for 5 days besides the above treatment. Then, 50 μg/L phorbol ester, 750 μg/L ionomycin and 20 mg/L brefeldin A were used to stimulate some cultured naive CD4+ T cells in the above groups. Flow cytometry was conducted to determine the proportion of CD4+CXCR5+PD-1+ cells and CD4+IL-21+ cells. Statistical analysis was carried out with SPSS20.0 software by using one-way analysis of variance (ANOVA) and student t test for the comparison of quantitative data between groups. Results The baicalin treatment could effectively improve the kidney impairment in the lupus-prone mice. Compared with the control group, the baicalin group showed significantly decreased 24-hour urine protein level ([1 416 ± 171] vs. [2 623 ± 278] μg/24 h, P = 0.022) , and significantly decreased proportion of Tfh cells in the spleen (12.6% ± 2.3% vs. 40.2% ± 1.1%, P = 0.005) . In vitro baicalin could further inhibit the differentiation of Tfh cells. Compared with the induction group, the intervention group showed significantly decreased proportion of CD4+CXCR5+PD-1+ Tfh cells (13.3% ± 0.8% vs. 17.6% ± 0.9%, P = 0.04) and CD4+IL-21+ cells (1.0% ± 0.4% vs. 2.7% ± 0.2%, P < 0.01) . Conclusion Baicalin can effectively ameliorate lupus nephritis, which may be associated with the inhibition of Tfh cell differentiation. Key words: Lupus erythematosus, systemic; Lupus nephritis; Baicalin; Disease models, animal; Follicular helper T cells; Interleukin-21

Therapeutic effect of baicalin on experimental autoimmune encephalomyelitis is mediated by SOCS3 regulatory pathway.

Natural compounds derived from medicinal plants have long been considered a rich source of novel therapeutic agents. Baicalin (Ba) is a bioactive flavonoid compound derived from the root of Scutellaria baicalensis, an herb widely used in traditional medicine for the treatment of various inflammatory diseases. In this study, we investigate the effects and mechanism of action of Ba in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Ba treatment effectively ameliorated clinical disease severity in myelin oligodendrocyte glycoprotein (MOG)35–55 peptide-induced EAE, and reduced inflammation and demyelination of the central nervous system (CNS). Ba reduced infiltration of immune cells into the CNS, inhibited expression of proinflammatory molecules and chemokines, and prevented Th1 and Th17 cell differentiation via STAT/NFκB signaling pathways. Further, we showed that SOCS3 induction is essential to the effects of Ba, given that the inhibitory effect of Ba on pathogenic Th17 responses was largely abolished when SOCS3 signaling was knocked down. Taken together, our findings demonstrate that Ba has significant potential as a novel anti-inflammatory agent for therapy of autoimmune diseases such as MS.

Baicalin may have a therapeutic effect in attention deficit hyperactivity disorder

Baicalin is a flavonoid purified from Scutellaria baicalensis Georgi. It possesses a variety of pharmacological properties, such as anti-inflammatory, antioxidant, antiapoptotic, and neuro-protective properties, and provides protection against cerebral hemorrhage. However, it is seldom considered a therapeutic in mental disorders. Recent studies showed that baicalin protects cerebral functions against ischemia and has sedative and anxiolytic-like effects. Animal experiments showed that it protects dopaminergic neurons in the striatum, hippocampus and substantia nigra. It also has effects such as anti-depressive and anti-epileptic and offers resistance to Parkinson’s disease. Attention deficit hyperactivity disorder (ADHD) pathogenesis is closely related to dopamine deficiency. However, the therapeutic effect of baicalin in ADHD has not been studied. We hypothesize that baicalin may protect dopaminergic neurons and increase brain dopamine levels, thus serving as an effective novel treatment for ADHD.

Baicalin attenuates alzheimer-like pathological changes and memory deficits induced by amyloid β1-42 protein.

Baicalin is one bioactive flavone with anti-inflammatory and neuroprotective activities. The neuroprotective effects of baicalin on pathological changes and behavioral deficits were explored in a mouse model of amyloid β (Aβ)(1-42) protein-induced Alzheimer's disease (AD). Mice received a bilateral injection of Aβ(1-42) protein into the hippocampus, then they were treated with baicalin (30, 50 and 100 mg/kg body weight, orally) or Tween 80. The therapeutic effects of baicalin were monitored by Morris water maze trial and probe test. Then mice were sacrificed for immunohistochemistry and western blot analysis. After a relatively short-term treatment of 14 days, 100 mg/kg of baicalin significantly ameliorated memory impairment in the Morris water maze test and probe test, and also attenuated glial cell activations and increase of TNF-α and IL-6 expressions induced by Aβ(1-42) protein. These results suggest that baicalin ameliorated Aβ(1-42) protein-related pathology and cognitive dysfunction via its anti-neuroinflammatory activity, and may be a potential candidate for the treatment of AD.

Baicalin Improves Survival in a Murine Model of Polymicrobial Sepsis via Suppressing Inflammatory Response and Lymphocyte Apoptosis

BackgroundAn imbalance between overwhelming inflammation and lymphocyte apoptosis is the main cause of high mortality in patients with sepsis. Baicalin, the main active ingredient of the Scutellaria root, exerts anti-inflammatory, anti-apoptotic, and even antibacterial properties in inflammatory and infectious diseases. However, the therapeutic effect of baicalin on polymicrobial sepsis remains unknown.Methodology/Principal FindingsPolymicrobial sepsis was induced by cecal ligation and puncture (CLP) in C57BL/6 mice. Mice were infused with baicalin intraperitoneally at 1 h, 6 h and 12 h after CLP. Survival rates were assessed over the subsequent 8 days. Bacterial burdens in blood and peritoneal cavity were calculated to assess the bacterial clearance. Neutrophil count in peritoneal lavage fluid was also calculated. Injuries to the lung and liver were detected by hematoxylin and eosin staining. Levels of cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10 and IL-17, in blood and peritoneum were measured by enzyme-linked immunosorbent assay. Adaptive immune function was assessed by apoptosis of lymphocytes in the thymus and counts of different cell types in the spleen. Baicalin significantly enhanced bacterial clearance and improved survival of septic mice. The number of neutrophils in peritoneal lavage fluid was reduced by baicalin. Less neutrophil infiltration of the lung and liver in baicalin-treated mice was associated with attenuated injuries to these organs. Baicalin significantly reduced the levels of proinflammatory cytokines but increased the level of anti-inflammatory cytokine in blood and peritoneum. Apoptosis of CD3+ T cell was inhibited in the thymus. The numbers of CD4+, CD8+ T lymphocytes and dendritic cells (DCs) were higher, while the number of CD4+CD25+ regulatory T cells was lower in the baicalin group compared with the CLP group.Conclusions/SignificanceBaicalin improves survival of mice with polymicrobial sepsis, and this may be attributed to its antibacterial property as well as its anti-inflammatory and anti-apoptotic effects.

Therapeutic Effects of Baicalin on Lipopolysaccharide-Induced Acute Lung Injury in Rats

Baicalin is a flavonoid present in many traditional Chinese medicines. A number of studies show that baicalin has anti-inflammatory actions and protects against a variety of tissue and organ injuries. The effect of baicalin in lipopolysaccharide (LPS)-induced acute lung injury is not well studied. In this study, typically acute lung injury was induced in rat by intratracheal injection of LPS, which increased lactate dehydrogenase activity and protein content in bronchoalveolar lavage fluid, wet/dry lung weight ratio, Evan's blue dye leakage, and neutrophil infiltration. Baicalin (20 mg/kg) was administrated 1 hour before or 30 min after LPS injection. Both pre and post-treatment with baicalin attenuated the increase of these parameters and improved histological finding. Our results suggest that baicalin has a therapeutic effect on LPS-induced acute lung injury.