Potential therapeutic effects of baicalin and baicalein.

Objective: Baicalin and baicalein are natural flavonoids reported for the first time from Scutellaria baicalensis Georgi. Recently, attention has been paid to these valuable flavonoids due to their promising effects. This paper aims to have a comprehensive review of their pharmacological effects. Materials and Methods: An extensive search through scientific databases including Scopus, PubMed, and ISI Web of Science was established. Results: According to literature, these compounds have been mainly effective in the treatment of neurological and neurodegenerative diseases, hepatic and cardiovascular disorders, metabolic syndrome, and cancers through anti-inflammatory and antioxidant pathways. Induction of apoptosis and autophagy, and inhibition of migration and metastasis are the main mechanisms for their cytotoxic and antitumor activities. Decreasing inflammation, reducing oxidative stress, regulating the metabolism of lipids, and decreasing fibrosis, apoptosis, and steatosis are their main hepatoprotective mechanisms. Inhibiting the development of cardiac fibrosis and reducing inflammation, oxidative stress, and apoptosis are also the mechanisms suggested for cardioprotective activities. Decreasing the accumulation of inflammatory mediators and improving cognitive function and depressive-like behaviours are the main mechanisms for neurological and neurodegenerative activities. Conclusion: The findings suggest the therapeutic potential of baicalin and baicalein. However, complementary research in different in vitro and in vivo models to investigate their mechanisms of action as well as clinical trials to evaluate their efficacy and safety are suggested.

Baicalin reduced injury of and autophagy-related gene expression in RAW264.7 cells infected with H6N6 avian influenza virus.

In the present study, we investigated whether baicalin could reduce the damage caused to RAW264.7 cells following infection with H6N6 avian influenza virus. In addition, we studied the expression of autophagy-related genes. The morphological changes in cells were observed by hematoxylin and eosin (H&E) staining, and the inflammatory factors in the cell supernatant were detected by enzyme-linked immunosorbent assay (ELISA). Transmission electron microscopy (TEM) was used to detect the levels of RAW264.7 autophagosomes, and western blotting and immunofluorescence were used to detect the protein expression of autophagy marker LC3. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to detect the mRNA transcription levels of autophagy key factors. The results showed that different doses of baicalin significantly reduced the H6N6 virus-induced damage of RAW264.7 cells. The contents of interleukin (IL)-1ß, IL-2, IL-6, and tumor necrosis factor (TNF)-α in the cell supernatant significantly decreased. In addition, the protein expression of LC3 and Beclin-1, ATG12, ATG5 the mRNA levels were significantly decreased. This study showed that baicalin can reduce cell damage and affect the H6N6-induced autophagy level of RAW264.7 cells.

Baicalin protects against hepatocyte injury caused by aflatoxin B1 via the TP53-related ferroptosis Pathway.

OBJECTIVE: Baicalin has antioxidative, antiviral, and anti-inflammatory properties. However, its ability to alleviate oxidative stress (OS) and DNA damage in liver cells exposed to aflatoxin B1 (AFB1), a highly hepatotoxic compound, remains uncertain. In this study, the protective effects of baicalin on AFB1-induced hepatocyte injury and the mechanisms underlying those effects were investigated. METHODS: Stable cell lines expressing CYP3A4 were established using lentiviral vectors to assess oxidative stress levels by conducting assays to determine the content of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Additionally, DNA damage was evaluated by 8-hydroxy-2-deoxyguanosine (8-OHdG) and comet assays. Transcriptome sequencing, molecular docking, and in vitro experiments were conducted to determine the mechanisms underlying the effects of baicalin on AFB1-induced hepatocyte injury. In vivo, a rat model of hepatocyte injury induced by AFB1 was used to evaluate the effects of baicalin. RESULTS: In vitro, baicalin significantly attenuated AFB1-induced injury caused due to OS, as determined by a decrease in ROS, MDA, and SOD levels. Baicalin also considerably decreased AFB1-induced DNA damage in hepatocytes. This protective effect of baicalin was found to be closely associated with the TP53-mediated ferroptosis pathway. To elaborate, baicalin physically interacts with P53, leading to the suppression of the expression of GPX4 and SLC7A11, which in turn inhibits ferroptosis. In vivo findings showed that baicalin decreased DNA damage and ferroptosis in AFB1-treated rat liver tissues, as determined by a decrease in the expression of γ-H2AX and an increase in GPX4 and SLC7A11 levels. Overexpression of TP53 weakened the protective effects of baicalin. CONCLUSIONS: Baicalin can alleviate AFB1-induced OS and DNA damage in liver cells via the TP53-mediated ferroptosis pathway. In this study, a theoretical foundation was established for the use of baicalin in protecting the liver from the toxic effects of AFB1.

The therapeutic effect of baicalin in the treatment of bladder cancer: a mini-review.

Bladder cancer (BC) is one of the most common challenges endangering public health worldwide. Therefore, finding effective ways to prevent and treat this disease can significantly reduce the detrimental effects of BC. Baicalein is a compound derived from the root of Scutellaria baicalensis. This compound possesses anticancer potential because numerous studies have confirmed its effectiveness in improving breast, liver, colon, leukaemia, skin, and lung cancers. In this study, we focused on reviewing the latest research on the therapeutic effects of baicalein in treating BC. According to our findings in this review, baicalein, by affecting various signalling pathways such as AKT, MAPK, Survivin/CDC2, MMP, Bax/Bcl2, NF-kB, and Drp1, inducing cell death, and halting cellular growth in cancer cells, can be an appealing therapeutic approach in treating BC.

Baicalin attenuated oxidative stress and inflammation in ethylene glycol-induced urolithiasis in adult male SD rats.

AIMS: Baicalin is a flavonoid derived from the root of the medicinal plant Scutellaria baicalensis Georgi (S. baicalensis) and is known for its various pharmacological properties. This study aimed to investigate the impact of baicalin (BAI) on the occurrence of kidney calcium oxalate crystal formation induced by ethylene glycol in male SD rats. MAIN METHODS: A rat model of renal stones was created and various concentrations of baicalin were used for intervention. Samples of urine, blood, and kidney tissue were taken from the rats, and they were euthanized for biochemical and histopathological examinations. KEY FINDINGS: Our results show that baicalin treatment improved the weight loss induced by ethylene glycol (EG) and ammonium chloride (AC) in rats. Baicalin also reduced the formation of calcium oxalate crystals and protected kidney function in rats with urolithiasis. Furthermore, it lowered the level of malondialdehyde (MDA) and elevated the activity of antioxidant enzymes compared to the stone control group. Additionally, baicalin notably alleviated renal inflammation in rats with urolithiasis. SIGNIFICANCE: The present study attributed clinical evidence first time that claiming the significant antiurolithic effect of baicalin and could be a cost-effective candidate for the prevention and treatment of urolithiasis.

Antiviral activity and underlying mechanisms of baicalin against porcine reproductive and respiratory syndrome virus in vitro.

Porcine reproductive and respiratory syndrome (PRRS) is a major challenge for the global swine industry, causing huge economic losses worldwide. To date, there are no effective measures to prevent and control the spread of PRRS virus (PRRSV). Baicalin (BA) is a natural flavonoid with various pharmacological effects, including antiviral, anti-inflammatory, antioxidant and immunomodulatory. Here, we demonstrate that BA exhibits potent anti-PRRSV activity in vitro, BA concentrations in the range of 5-20 µg/mL significantly inhibited PRRSV infection in a dose-dependent manner and were independent of PRRSV strain. Mechanistically, BA inhibited PRRSV replication by directly interacting with virions, thereby affecting multiple stages of the virus life cycle. Meanwhile, the preventive effect of BA on PRRSV could be realized by inhibiting CD151 and CD163 expression. Furthermore, BA reduced the PRRSV-induced expression of PAMs cytokines (IFN-α, IL-6, IL-8, and TNF-α), suggesting that BA-induced antiviral cytokines may help BA inhibit PRRSV infection. Taken together, BA can be used as an inhibitor of PRRSV infection in vitro, which provides a theoretical basis for the clinical application of BA and the prevention and control of PRRSV infection, which is worthy of further in vivo studies in swine.

Baicalin and Baicalein Enhance Cytotoxicity, Proapoptotic Activity, and Genotoxicity of Doxorubicin and Docetaxel in MCF-7 Breast Cancer Cells.

Breast cancer is a major health concern and the leading cause of death among women worldwide. Standard treatment often involves surgery, radiotherapy, and chemotherapy, but these come with side effects and limitations. Researchers are exploring natural compounds like baicalin and baicalein, derived from the Scutellaria baicalensis plant, as potential complementary therapies. This study investigated the effects of baicalin and baicalein on the cytotoxic, proapoptotic, and genotoxic activity of doxorubicin and docetaxel, commonly used chemotherapeutic drugs for breast cancer. The analysis included breast cancer cells (MCF-7) and human endothelial cells (HUVEC-ST), to assess potential effects on healthy tissues. We have found that baicalin and baicalein demonstrated cytotoxicity towards both cell lines, with more potent effects observed in baicalein. Both flavonoids, baicalin (167 µmol/L) and baicalein (95 µmol/L), synergistically enhanced the cytotoxic, proapoptotic, and genotoxic activity of doxorubicin and docetaxel in breast cancer cells. In comparison, their effects on endothelial cells were mixed and depended on concentration and time. The results suggest that baicalin and baicalein might be promising complementary agents to improve the efficacy of doxorubicin and docetaxel anticancer activity. However, further research is needed to validate their safety and efficacy in clinical trials.

Effects of a Dietary Supplement Composed of Baicalin, Bromelain and Escin for Venous Chronic Insufficiency Treatment: Insights from a Retrospective Observational Study.

Chronic venous insufficiency (CVI) represents a risk factor for cardiovascular events. The first-line treatment includes the use of compression stockings and lifestyle changes. Natural products, such as flavonoids, could be used to improve the effects of compression therapy due to their anti-inflammatory and anti-oxidant properties. This study aims to evaluate the effects of a dietary supplement containing baicalin, bromeline and escin in CVI patients. A retrospective cohort study was performed by using the medical records of CVI affected outpatients. Patients treated with the dietary supplement were defined as "users". A modified Venous Clinical Severity Score (VCSS) was calculated, including pain, inflammation, vessels induration and skin pigmentation. All clinical variables were evaluated at baseline (T0), after 30 (T1) and 90(T2) days in "users" and "non-users". Out of 62 patients, 30 (48.4%) were "users". No difference was observed between groups at baseline. A lower VCSS value was recorded in "users" than that observed in "non-users" at T2 (7.0 (4.0-9.0) vs. 9.0 (5.0-10.0); p = 0.025). Vessels' induration and pain significantly reduced in 53.3% and 43.3% of "users" and in 18.8% and 9.4% of "non-users". Only "users" (33.3%) showed a reduction of the inflammatory signs as well as a decrease in malleolar circumference, from 29.0 (26.5-30.0) to 27.5 (26.0-28.5) (p < 000.1). A reduction of C-reactive Protein levels was found in "users" compared to "non-users" at T2 (1.0 (0.9-1.2) vs. 1.3 (1.0-1.5); p = 0.006). These findings suggest that implementation of a dietary supplement could improve the clinical outcomes of CVI patients.

Study on the Effect of Pharmaceutical Excipient PEG400 on the Pharmacokinetics of Baicalin in Cells Based on MRP2, MRP3, and BCRP Efflux Transporters.

Pharmaceutical excipient PEG400 is a common component of traditional Chinese medicine compound preparations. Studies have demonstrated that pharmaceutical excipients can directly or indirectly influence the disposition process of active drugs in vivo, thereby affecting the bioavailability of drugs. In order to reveal the pharmacokinetic effect of PEG400 on baicalin in hepatocytes and its mechanism, the present study first started with the effect of PEG400 on the metabolic disposition of baicalin at the hepatocyte level, and then the effect of PEG400 on the protein expression of baicalin-related transporters (BCRP, MRP2, and MRP3) was investigated by using western blot; the effect of MDCKII-BCRP, MDCKII-BCRP, MRP2, and MRP3 was investigated by using MDCKII-BCRP, MDCKII-MRP2, and MDCKII-MRP3 cell monolayer models, and membrane vesicles overexpressing specific transporter proteins (BCRP, MRP2, and MRP3), combined with the exocytosis of transporter-specific inhibitors, were used to study the effects of PEG400 on the transporters in order to explore the possible mechanisms of its action. The results demonstrated that PEG400 significantly influenced the concentration of baicalin in hepatocytes, and the AUC0-t of baicalin increased from 75.96 ± 2.57 µg·h/mL to 106.94 ± 2.22 µg·h/mL, 111.97 ± 3.98 µg·h/mL, and 130.42 ± 5.26 µg·h/mL (p ˂ 0.05). Furthermore, the efflux rate of baicalin was significantly reduced in the vesicular transport assay and the MDCKII cell model transport assay, which indicated that PEG400 had a significant inhibitory effect on the corresponding transporters. In conclusion, PEG400 can improve the bioavailability of baicalin to some extent by affecting the efflux transporters and thus the metabolic disposition of baicalin in the liver.

Protective effects of baicalin against phenylarsine oxide-induced cytotoxicity in human skin keratinocytes.

Phenylarsine oxide (PAO) is a known environmental pollutant and skin keratinocytes are most seriously affected. Baicalin (BCN) was reported to have antioxidant and anti-inflammatory effects, but its protective effect against PAO toxicity is unknown. This study aimed at exploring whether baicalin can reverse the toxicity of human epidermal keratinocytes that are subjected to PAO exposure and underlying mechanisms. In silico analysis from a publicly accessible HaCaT cell transcriptome dataset exposed to chronic Arsenic showed significant differential expression of several genes, including the genes related to DNA replication. Later, we performed in vitro experiments, in which HaCaT cells were exposed to PAO (500 nM) in the existence of BCN (10-50 µM). Treatment of PAO alone induces the JNK, p38 and caspase-3 activation, which were engaged in the apoptosis induction, while the activity of AKT was significantly inhibited, which was engaged in the suppression of apoptosis. PAO suppressed SIRT3 expression and induced intracellular reactive oxygen species (ROS), causing a marked reduce in cell viability and apoptosis. However, BCN treatment restored the PAO-induced suppression of SIRT3 and AKT expression, reduced intracellular ROS generation, and markedly suppressed both caspase-3 activation and apoptosis induction. However, the protective effect of BCN was significantly attenuated after pretreatment with nicotinamide, an inhibitor of SIRT3. These findings indicate that BCN protects against cell death induced by PAO via inhibiting excessive intracellular ROS generation via restoring SIRT3 activity and reactivating downstream AKT pathway. In this study, we firstly shown that BCN is an efficient drug to prevent PAO-induced skin cytotoxicity, and these findings need to be confirmed by in vivo and clinical investigations.

Baicalin-loaded Polydopamine modified ZIF-8 NPs inhibits myocardial ischemia/reperfusion injury in rats.

Baicalin (BAN) has shown promise in alleviating myocardial ischemia/reperfusion (I/R) injury, yet its limited solubility and biocompatibility have hindered its application. Developing drug delivery systems is a promising strategy to enhance the therapeutic potential of BAN in the context of I/R injury. This study aims to prepare a BAN-loaded nanodrug system using polydopamine (PDA)-modified Zeolitic imidazolate framework-8 (ZIF-8) as a carrier, with the goal of improving BAN's mitigating effects on I/R injury. We prepared the BAN nanoparticles (NPs) system, PZB NPs, using ZIF-8 as the carrier. The system was characterized in terms of morphology, particle size, zeta potential, and X-ray diffraction (XRD). We assessed the cytotoxicity of PZB NPs in H9c2 cells, investigated its effects and mechanisms in H/R-induced H9c2 cells, and evaluated its ability to alleviate myocardial I/R injury in rats. PZB NPs exhibited good dispersion, with a BAN loading efficiency of 26.43 ± 1.55%, a hydrated particle size of 102.21 ± 1.19 nm, and a zeta potential of -24.84 ± 0.07 mV. It displayed slow and sustained drug release in an acidic environment (pH 5.5). In vitro studies revealed that PZB NPs was non-cytotoxic and significantly enhanced the recovery of H/R injury H9c2 cell viability. PZB NPs suppressed cell apoptosis, activated the Nrf2/HO-1 pathway, and cleared ROS. In vivo study demonstrated that PZB NPs significantly reduced infarct size, ameliorated fibrosis and improved heart function. The PZB NPs markedly enhances BAN's ability to alleviate I/R injury, both in vitro and in vivo, offering a promising drug delivery system for clinical applications.

Baicalin attenuates aflatoxin B1-induced hepatotoxicity via suppressing c-Jun-N-terminal kinase-mediated cell apoptosis.

Aflatoxin B1 (AFB1) is classified as a Class I carcinogen and common pollutant in human and animal food products. Prolonged exposure to AFB1 can induce hepatocyte apoptosis and lead to hepatotoxicity. Therefore, preventing AFB1-induced hepatotoxicity remains a critical issue and is of great significance. Baicalin, a polyphenolic compound derived from Scutellaria baicalensis Georgi, has a variety of pharmacodynamic activities, such as antiapoptotic and anticancer activities. This study systematically investigated the alleviating effect of baicalin on AFB1-induced hepatotoxicity from the perspective of apoptosis and explored the possible molecular mechanism. In the normal human liver cell line L02, baicalin treatment significantly inhibited AFB1-induced c-Jun-N-terminal Kinase (JNK) activation and cell apoptosis. In addition, the in vitro mechanism study demonstrated that baicalin alleviates AFB1-induced hepatocyte apoptosis through suppressing the translocation of phosphorylated JNK to the nucleus and decreasing the phosphorylated c-Jun/c-Jun ratio and the Bax/Bcl2 ratio. Molecular docking and drug affinity responsive target stability assays demonstrated that baicalin has the potential to target JNK. This study provides a basis for the therapeutic effect of baicalin on hepatocyte apoptosis caused by AFB1, indicating that the development of baicalin and JNK pathway inhibitors has broad application prospects in the prevention of hepatotoxicity, especially hepatocyte apoptosis.

Baicalin Prevents Colon Cancer by Suppressing CDKN2A Protein Expression.

OBJECTIVE: To observe the therapeutic effects and underlying mechanism of baicalin against colon cancer. METHODS: The effects of baicalin on the proliferation and growth of colon cancer cells MC38 and CT26. WT were observed and predicted potential molecular targets of baicalin for colon cancer therapy were studied by network pharmacology. Furthermore, molecular docking and drug affinity responsive target stability (DARTS) analysis were performed to confirm the interaction between potential targets and baicalin. Finally, the mechanisms predicted by in silico analyses were experimentally verified in-vitro and in-vivo. RESULTS: Baicalin significantly inhibited proliferation, invasion, migration, and induced apoptosis in MC38 and CT26 cells (all P<0.01). Additionally, baicalin caused cell cycle arrest at the S phase, while the G0/G1 phase was detected in the tiny portion of the cells. Subsequent network pharmacology analysis identified 6 therapeutic targets associated with baicalin, which potentially affect various pathways including 39 biological processes and 99 signaling pathways. In addition, molecular docking and DARTS predicted the potential binding of baicalin with cyclin dependent kinase inhibitor 2A (CDKN2A), protein kinase B (AKT), caspase 3, and mitogen-activated protein kinase (MAPK). In vitro, the expressions of CDKN2A, MAPK, and p-AKT were suppressed by baicalin in MC38 and CT26 cells. In vivo, baicalin significantly reduced the tumor size and weight (all P<0.01) in the colon cancer mouse model via inactivating p-AKT, CDKN2A, cyclin dependent kinase 4, cyclin dependent kinase 2, interleukin-1, tumor necrosis factor α, and activating caspase 3 and mouse double minute 2 homolog signaling (all P<0.05). CONCLUSION: Baicalin suppressed the CDKN2A protein level to prevent colon cancer and could be used as a therapeutic target for colon cancer.

Baicalin nanodelivery system based on functionalized metal-organic framework for targeted therapy of osteoarthritis by modulating macrophage polarization.

Intra-articular drugs used to treat osteoarthritis (OA) often suffer from poor pharmacokinetics and stability. Nano-platforms as drug delivery systems for drug delivery are promising for OA therapy. In this study, we reported an M1 macrophage-targeted delivery system Bai@FA-UIO-66-NH2 based on folic acid (FA) -modified metal-organic framework (MOF) loaded with baicalin (Bai) as antioxidant agent for OA therapy. With outstanding biocompatibility and high drug loading efficiency, Bai@FA-UIO-66-NH2 could be specifically uptaken by LPS-induced macrophages to serve as a potent ROS scavenger, gradually releasing Bai at the subcellular level to reduce ROS production, modulate macrophage polarization to M2, leading to alleviation of synovial inflammation in OA joints. The synergistic effect of Bai@FA-UIO-66-NH2 on macrophage polarization and ROS scavenging significantly improved the therapeutic efficacy of OA, which may provide a new insight into the design of OA precision therapy.

Baicalin enhances the chemotherapy sensitivity of oxaliplatin-resistant gastric cancer cells by activating p53-mediated ferroptosis.

Gastric cancer is one of the most common malignant tumors, and chemotherapy is the main treatment for advanced gastric cancer. However, chemotherapy resistance leads to treatment failure and poor prognosis in patients with gastric cancer. Multidrug resistance (MDR) is a major challenge that needs to be overcome in chemotherapy. According to recent research, ferroptosis activation is crucial for tumor therapeutic strategies. In this work, we explored the solution to chemoresistance in gastric cancer by investigating the effects of the Chinese medicine monomer baicalin on ferroptosis. Baicalin with different concentrations was used to treat the parent HGC27 and drug-resistant HGC27/L cells of gastric cancer. Cell viability was measured by CCK8, and synergistic effects of baicalin combined with oxaliplatin were evaluated using Synergy Finder software. The effects of baicalin on organelles and cell morphology were investigated using projective electron microscopy. Iron concentration, MDA production and GSH inhibition rate were measured by colorimetry. ROS accumulation was detected by flow cytometry. The ferroptosis-related genes (IREB2, TfR, GPX4, FTH1), P53, and SLC7A11 were analysed by Western blot, and the expression differences of the above proteins between pretreatment and pretreatment of different concentrations of baicalin, were assayed in both parental HGC27 cells and Oxaliplatin-resistant HGC27/L cells. Mechanically, Baicalin disrupted iron homeostasis and inhibits antioxidant defense, resulting in iron accumulation, lipid peroxide aggregation, and specifically targeted and activated ferroptosis by upregulating the expression of tumor suppressor gene p53, thereby activating the SLC7A11/GPX4/ROS pathway mediated by it. Baicalin activates ferroptosis through multiple pathways and targets, thereby inhibiting the viability of oxaliplatin-resistant gastric cancer HGC27/L cells and enhancing the sensitivity to oxaliplatin chemotherapy.

Effects of baicalin pre-treatment on pentylenetetrazole-induced seizures: Insights from zebrafish larvae locomotor behavior and neuronal calcium imaging.

Natural compounds are increasingly being studied for their potential neuroprotective effects against inflammatory neurological diseases. Epilepsy is a common neurological disease associated with inflammatory processes, and around 30% of people with epilepsy do not respond to traditional treatments. Some flavonoids, when taken along with antiseizure medications can help reduce the likelihood of drug-resistant epilepsy. Baicalin, a plant-based compound, has been shown to possess pharmacological properties such as anti-inflammatory, neuroprotective, anticonvulsant, and antioxidant activities. In this study, we tested the effect of baicalin on an established model of pharmacologically induced seizure in zebrafish using measures of both locomotor behavior and calcium imaging of neuronal activity. The results of our study showed that, at the tested concentration, and contrary to other studies in rodents, baicalin did not have an anti-seizure effect in zebrafish larvae. However, given its known properties, other concentrations and approaches should be explored to determine if it could potentially have other beneficial effects, either alone or when administered in combination with classic antiseizure medications.

Baicalin suppresses macrophage JNK-mediated adipose tissue inflammation to mitigate insulin resistance in obesity.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix scutellariae (the root of Scutellaria baicalensis Georgi) is a traditional Chinese medicine (TCM) used to treat a wide range of inflammation-related diseases, such as obesity, diabetes, diabetic kidney disease, and COVID-19-associated inflammatory states in the lung and kidney. Baicalin is the major anti-inflammatory component of Radix scutellariae and has shown the potential to inhibit inflammation in metabolic disorders. In this study, we explored the ability and underlying mechanisms of baicalin to modulate the macrophage to mitigate insulin resistance in obesity. MATERIALS AND METHODS: Obese mice were administered baicalin (50 mg/kg/day) intraperitoneally for 3 weeks. RAW264.7 and BMDM cells were stimulated with LPS and treated with baicalin for 24 h, while 3T3-L1 and primary white adipocytes were treated with the supernatants from baicalin-treated RAW264.7 cells for 24 h. RESULTS: The results showed that baicalin significantly improved glucose and insulin tolerance as well as decreased fat and adipose tissue macrophage levels in obese mice. Besides, baicalin significantly reduced serum and adipose tissue IL-1ß, TNF-α and IL-6 levels in obese mice, as well as suppressed LPS-induced IL-1ß, TNF-α and IL-6 expression and release in macrophages. Furthermore, treatment with the supernatant from baicalin-treated RAW264.7 cells increased the levels of PGC-1α, SIRT1, p-IRS-1 and p-AKT in adipocytes. Moreover, baicalin treatment dramatically downregulated macrophage p-p38, p-JNK, and Ac-p65Lys310 levels while increasing SIRT1 both in vivo and in vitro. Importantly, JNK inhibitor SP600125 blocked most of the effects of baicalin on SIRT1, Ac-p65Lys310 and pro-inflammatory factors in macrophages. CONCLUSION: Therefore, these results demonstrated for the first time that baicalin exerts its anti-inflammatory effects in obese adipose tissue macrophages mainly through suppressing JNK/SIRT1/p65 signaling. These findings amplified the mechanisms of baicalin and its potential to attenuate insulin resistance.

Baicalin attenuates acute skin damage induced by ultraviolet B via inhibiting pyroptosis.

As the outermost layer of the human body, the skin suffers from various external factors especially light damage, among which ultraviolet B (UVB) irradiation is common and possesses a relatively high biological damage capacity. Pyroptosis is a newly discovered type of programmed cell death, which can induce cell rupture and induce local inflammatory response. However, the molecular mechanisms of pyroptosis in photodamaged skin is poorly understood. Baicalin, a flavonoid extracted from the desiccated root of Scutellaria baicalensis Georgi (Huang Qin). Despite its antioxidant abilities, whether baicalin protects skin by attenuating UVB-induced pyroptosis remains unclear, which was the aim of this study. The UVB-induced acute skin damage model was established by using human immortalized keratinocytes (HaCaT cells) and Kunming (KM) strain mice. The protective dose selection for baicalin is 50 µM in vitro and 100 mg/kg in vivo. In in vitro study, UVB irradiation significantly decreased cell viability, increased cell death and oxidative stress in HaCaT cells, while pretreatment with baicalin improved these phenomena. Furthermore, the baicalin pretreatment notably suppressed nuclear factor kappa B (NF-κB) translocation, the NLRP3 inflammasome activation and gasdermin D (GSDMD) maturation, thus effectively attenuating UVB-induced pyroptosis. In in vivo study, the baicalin pretreatment mitigated epidermal hyperplasia, collagen fiber fragmentation, oxidative stress and pyroptosis in UVB-irradiated mouse skin. In a nutshell, this study suggests that baicalin could be a potential protective agent to attenuate acute skin damage induced by UVB irradiation through decreasing oxidative stress and suppressing NF-κB/NLRP3/GSDMD-involved pyroptosis.

Baicalin alleviates angiotensin II-induced cardiomyocyte apoptosis and autophagy and modulates the AMPK/mTOR pathway.

As a main extraction compound from Scutellaria baicalensis Georgi, Baicalin exhibits various biological activities. However, the underlying mechanism of Baicalin on hypertension-induced heart injury remains unclear. In vivo, mice were infused with angiotensin II (Ang II; 500 ng/kg/min) or saline using osmotic pumps, followed by intragastrically administrated with Baicalin (5 mg/kg/day) for 4 weeks. In vitro, H9C2 cells were stimulated with Ang II (1 µM) and treated with Baicalin (12.5, 25 and 50 µM). Baicalin treatment significantly attenuated the decrease in left ventricular ejection fraction and left ventricular fractional shortening, increase in left ventricular mass, left ventricular systolic volume and left ventricular diastolic volume of Ang II infused mice. Moreover, Baicalin treatment reversed 314 differentially expressed transcripts in the cardiac tissues of Ang II infused mice, and enriched multiple enriched signalling pathways (including apoptosis, autophagy, AMPK/mTOR signalling pathway). Consistently, Baicalin treatment significantly alleviated Ang II-induced cell apoptosis in vivo and in vitro. Baicalin treatment reversed the up-regulation of Bax, cleaved-caspase 3, cleaved-caspase 9, and the down-regulation of Bcl-2. Meanwhile, Baicalin treatment alleviated Ang II-induced increase of autophagosomes, restored autophagic flux, and down-regulated LC3II, Beclin 1, as well as up-regulated SQSTM1/p62 expression. Furthermore, autophagy inhibitor 3-methyladenine treatment alleviated the increase of autophagosomes and the up-regulation of Beclin 1, LC3II, Bax, cleaved-caspase 3, cleaved-caspase 9, down-regulation of SQSTM1/p62 and Bcl-2 expression after Ang II treated, which similar to co-treatment with Baicalin. Baicalin treatment reduced the ratio of p-AMPK/AMPK, while increased the ratio of p-mTOR/mTOR. Baicalin alleviated Ang II-induced cardiomyocyte apoptosis and autophagy, which might be related to the inhibition of the AMPK/mTOR pathway.

Preparing a novel baicalin-loaded microemulsion-based gel for transdermal delivery and testing its anti-gout effect.

We previously demonstrated that baicalin had efficacy against gouty arthritis (GA) by oral administration. In this paper, a novel baicalin-loaded microemulsion-based gel (B-MEG) was prepared and assessed for the transdermal delivery of baicalin against GA. The preparation method and transdermal capability of B-MEG was screened and optimized using the central composite design, Franz diffusion cell experiments, and the split-split plot design. Skin irritation tests were performed in guinea pigs. The anti-gout effects were evaluated using mice. The optimized B-MEG comprised of 50 % pH 7.4 phosphate buffered saline, 4.48 % ethyl oleate, 31.64 % tween 80, 13.88 % glycerin, 2 % borneol, 0.5 % clove oil and 0.5 % xanthan gum, with a baicalin content of (10.42 ± 0.08) mg/g and particle size of (15.71 ± 0.41) nm. After 12 h, the cumulative amount of baicalin permeated from B-MEG was (672.14 ± 44.11) µg·cm-2. No significant skin irritation was observed following B-MEG application. Compared to the model group, B-MEG groups significantly decreased the rate of auricular swelling (P < 0.01) and number of twists observed in mice (P < 0.01); and also reduced the rate of paw swelling (P < 0.01) and inflammatory cell infiltration in a mouse model of GA. In conclusion, B-MEG represents a promising transdermal carrier for baicalin delivery and can be used as a potential therapy for GA.