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Berberine is the basic chemical component of a Chinese herb, Coptis chinensis Franch (coptis), considered to be useful in treating some diseases of the cardiovascular system, such as hypertension and chronic heart failure (CHF). In this study, we investigate the inhibitory effect of berberine on experimental cardiac hypertrophy, which is regarded as a risk factor of CHF and other heart diseases. Forty-two male SD rats were divided into four groups: age-matched control, aortic banding model, berberine-treated group and captopril-treated group. Cardiac hypertrophy was induced by suprarenal abdominal aorta constriction (banding). The drugs were orally administered for 8 weeks starting from 4 weeks after surgery at dosage of berberine 10 mg/kg and captopril 50 mg/kg. Blood pressure (BP) was measured four times during the period of the experiment, and hemodynamic parameters, cardiac index, cell size of left ventricular myocardium and total protein of left ventricular tissue were detected 8 weeks after treatment with drugs. The data from the present study showed that: (1) The BP of the aorta banded rats was increased compared with those of the normal (p < 0.001) and the age-matched control rats (p < 0.001), and berberine showed no significant effect on it. (2) After 8 weeks of treatment with berberine, the elevated left ventricular end diastolic pressure (LVEDP) was slightly decreased compared with the aortic banded rats. Meanwhile, the maximum rates of contraction and relaxation (±dp/dt_max) was increased (p < 0.05) and the time to reach the point of maximum rate from beginning of contraction (t-dp/dt) was shortened (p < 0.01), indicating that the functions of heart, both contraction and relaxation, were improved. (3) Cardiac growth was inhibited by treatment with berberine. Both whole heart and left ventricular weight were notably decreased compared with the banded rats (p < 0.05 and p < 0.01). (4) The cell size of left ventricular myocardium was significantly reduced (p < 0.001) and the total protein of left ventricular tissue was slightly down-regulated by treatment with berberine. These data suggest that berberine can improve abnormal cardiac function and can prevent the development of left ventricular hypertrophy induced by pressure overload. This indicates that it may have therapeutic potential in the treatment of CHF.

Much progress has been made in the pharmacology of Traditional Chinese Medicine (TCM). However, the question on how to investigate pharmacokinetics of TCM extract remains. In this study, we selected a new TCM extract YL2000 developed in our laboratory as the research object and investigated both the pharmacokinetics of baicalin and berberine in YL2000 and the pharmacodynamics of YL2000 in febrile rats. The correlation analysis between the time-concentration curves of baicalin and berberine and the time-effect curve of YL2000 was conducted in plasma by statistical methods. The results showed that the time-effect data of anti-pyretic effect of YL2000 had a negative correlation (r=-0.8312, P<0.1) with the time-concentration data of baicalin in plasma, but had no correlation (r=0.01368, P>0.5) with berberine. These data suggested that baicalin could be selected as a marker of anti-pyretic effect, and that YL2000 could be used to treat fevers according to the disposition of baicalin in vivo.

In this study, we also proposed that one or more active elements in TCM extracts could be selected to represent the pharmacokinetics of TCM extracts in vivo, combined with the pharmacodynamics of TCM extract.

A rapid and simple high-performance liquid chromatographic method for determination of berberine in rat thalamus was described in this study. Thalamus samples were pretreated by protein precipitation with methanol and acetonitrile. Berberine was determined using a Hypersil C₁₈ column with an isocratic mobile phase of acetonitrile — 0.05 M potassium dihydrogen phosphate (containing 0.5% triethylamine, pH 3.0) (30:70 v/v) and with UV detection at 265 nm. The lower limit of quantification for berberine in thalamus was 24 ng/ml, and the lowest concentration of berberine determined in rat thalamus samples was 47.5 ng/ml at 48 hours. The calibration curve for berberine was linear (r² = 0.9994) over the concentration range 24–6000 ng/ml. At this concentration range, the overall recoveries (91.20%–93.24%) for berberine were determined and the accuracy of the intra- and inter-day assays from rat thalamus were less than 6% RSD. Following intravenous administration of 10.2 mg/kg of Coptidis Rhizoma (CR) extract containing 3 mg/kg berberine into rats, the thalamus level of berberine increased rapidly (t_1/2α = 1.93 hours), peaked at 2.48 hours with a concentration of 271 ng/g, and had a slow elimination rate (t_1/2β = 14.6 hours), which suggested that berberine might directly act on certain regions of the thalamus, have pharmacological effects on some cerebral dysfunctions, and be an active ingredient of Huang Lian Jie Du Tang for the treatment of cerebral disease.

This study investigates the effects of beriberine on the expression of lectin-like ox-LDL receptor-1 (LOX-1), scavenger receptor A (SR-A), SR class B type I (SR-BI) and ATP-binding cassette transporter A1 (ABCA1) in human macrophage-derived foam cells induced by ox-LDL. Different concentrations of Berberine were co-cultured with THP-1 derived foam cells. The mRNA and protein expressions of LOX-1, SR-A, SR-BI and ABCA1 were determined by RT-PCR and Western blot analysis, respectively. Ox-LDL significantly increased the expression of LOX-1 and inhibited the expression of SR-BI in a dose- and time-dependent manner. Berberine significantly inhibited the effects of ox-LDL in a dose- and time-dependent manner. Moreover, ox-LDL significantly promoted ABCA1 expression. However, berberine had no effect on SR-A or ABCA1 expression. Berberine can inhibit the expression of LOX-1 and promote the expression of SR-BI in macrophage-derived foam cells. Therefore, berberine could be used to treat atherosclerotic diseases.

Diabetes is a major medical problem that imperils public health. Over two thousand years ago, Traditional Chinese Medicine (TCM) called diabetes-related symptoms "Xiaoke" disease. In ancient China, TCM and Chinese herbal medicines were used widely in treating Xiaoke and abundant experience has been accumulated. This article discusses the TCM theory on diabetes and its achievements in the prevention and treatment of diabetes in the past. Using Chinese herbal medicine, recent progress in diabetes therapeutics, including data from clinical trials, are presented. Mechanistic studies from basic research are discussed. Yin-yang balance and a holistic approach of TCM may complement diabetes treatment in Western medicine. With continuous efforts, TCM could play a more important role in fighting this disease.

Berberine (BBR) has been shown to attenuate the deleterious effects of ischemia/reperfusion (I/R) injury in the brain. We evaluated the effects of BBR on intestinal tight junction (TJ) changes during mesenteric I/R. I/R was induced in rats by the occlusion of the superior mesenteric artery and reperfusion. The rats were randomized into four groups: control, BBR, I/R, and I/R + BBR. Intestinal permeability was determined by the lactulose/mannitol test. The ileum and colon were harvested to assess mucosal injury and inducible nitric oxide synthase activity. The TJ ultrastructure was studied by transmission electron microscopy. The expressions and locations of the TJ proteins, occludin and ZO-1, in the epithelium were investigated by immunofluorescence microscopy. We also used Western blot analysis to detect the distribution of TJ proteins in lipid raft fractions. Our results suggest that I/R-induced intestinal TJ dysfunction can be improved by BBR, thereby demonstrating the therapeutic potential of BBR for intestinal I/R.

Berberine is an isoquinoline alkaloid present in several plant species, including Coptis sp. and Berberis sp. In traditional medicine, extracts of berberine are used in the treatment of diarrhea of different origins. Recent studies have shown that berberine and its derivatives have significant biological effects on gastrointestinal (GI) and other functions and may become therapeutics for the treatment of diarrhea, gastroenteritis, diabetes, hyperlipidemia, cardiovascular diseases and inflammatory conditions. This paper summarizes the current knowledge on the actions of berberine in the GI tract. Binding and target sites, activated intracellular pathways, as well as the absorption and metabolism of berberine are discussed. Effects that may be useful in future clinical treatment, like antidiarrheal, anti-inflammatory and antitumor effects are critically reviewed and potential clinical applications are presented in detail.

Berberine (BBR), an alkaloid component isolated from Chinese medicinal herb Huang Lian, has aroused broad interests for its antitumor effect in recent years. The signal transducer and activator of transcription 3 (STAT3), plays critical roles in malignant transformation and progression and was found to be constitutively activated in a variety of human cancers. In this study, we show that BBR inhibited cell proliferation, induced apoptosis, and suppressed tumor spheroid formation of lung cancer cell lines. These effects were correlated with BBR-mediated suppression of both phosphorylated and total levels of STAT3 protein. Furthermore, BBR promoted STAT3 degradation by enhancing ubiquitination. Importantly, we demonstrated that BBR was able to inhibit doxorubicin (DOX)-mediated STAT3 activation and sensitize lung cancer cells to the cytotoxic effect of DOX treatment. Given that BBR is widely used in clinic with low toxicity, our results are potentially important for the development of a novel combinatorial therapy with BBR and DOX in the treatment of lung cancer.

Berberine exerts neuroprotective and modulates hypoxia inducible factor-1-alpha (HIF-1$\alpha )$. Based on the role of HIF-1$\alpha$ in hypoxia preconditioning and association between HIF-1$\alpha$ and sphingosine-1-phosphate (S1P), we hypothesized that berberine preconditioning (BP) would ameliorate the cerebral injury induced by ischemia through activating the system of HIF-1$\alpha$ and S1P. Adult male rats with middle cerebral artery occlusion (MCAO) and rat primary cortical neurons treated with oxygen and glucose deprivation (OGD) with BP at 24h (40mg/kg) and 2h (10${}^{-6}$mol/L), respectively, were used to determine the neuroprotective effects. The HIF-1$\alpha$ accumulation, and S1P metabolism were assayed in the berberine-preconditioned neurons, and the HIF-1$\alpha$-mediated transcriptional modulation of sphingosine kinases (Sphk) 1 and 2 was analyzed using chromatin immunoprecipitation and real-time polymerase chain reaction. BP significantly prevented cerebral ischemic injury in the MCAO rats at 24h and 72h following ischemia/reperfusion. In OGD-treated neurons, BP enhanced HIF-1$\alpha$ accumulation with activation of PI3K/Akt, and induced S1P production by activating Sphk2 via the promotion of HIF-1$\alpha$-mediated Sphk2 transcription. In conclusion, BP activated endogenous neuroprotective mechanisms associated with the S1P/HIF-1 pathway and helped protect neuronal cells against hypoxia/ischemia.

Berberine (BBR), an isoquinoline alkaloid, is a well-known bioactive compound contained in medicinal plants used in traditional and folk medicines. In this study, we investigated the subcellular localization and the apoptotic mechanisms of BBR were elucidated. First, we confirmed the incorporation of BBR into the cell visually. BBR showed antiproliferative activity and promptly localized to the nucleus from 5min to 15min after BBR treatment in HL-60 human promyelocytic leukemia cells. Next, we examined the antiproliferative activity of BBR (1) and its biosynthetically related compounds (2-7) in HL-60 cells. BBR exerted strongest antiproliferative activity among 1-7 and the results of structures and activity relation suggested that a methylenedioxyl group in ring A, an $O$-alkyl group at C-9 position, and the frame of isoquinoline may be necessary for antiproliferative activity. Moreover, BBR showed the most potent antiproliferative activity in HL-60 cells among human cancer and normal cell lines tested. Next, we examined the effect of BBR on molecular events known as apoptosis induction. In HL-60 cells, BBR induced chromatin condensation and DNA fragmentation, and triggered the activation of PARP, caspase-3 and caspase-8 without the activation of caspase-9. BBR-induced DNA fragmentation was abolished by pretreatment with inhibitors against caspase-3 and caspase-8, but not against caspase-9. ERK and p38 were promptly phosphorylated after 15 min of BBR treatment, and this was correlated with time of localization to the nucleus of BBR. These results demonstrated that BBR translocated into nucleus immediately after treatments and induced apoptotic cell death by activation of caspase-3 and caspase-8.

In recent years, berberine has increasingly become a topic of research as a treatment for diabetes due to its repair function, which recovers damaged pancreatic β cells. However, it is the complications of diabetes that seriously affect patients’ life quality and longevity, among which diabetic neuropathy and the consequent acute pain are the most common. In this study, we established STZ-induced diabetic models to observe whether berberine, a main constitute of Coptis chinensis Franch which has shown good hypoglycemic effects, could relieve diabetes-induced pain and explored its possible mechanism in rats and mice. Behavior assays showed increasing mechanical allodynia and thermal hyperalgesia thresholds by the Von Frey test and tail flick test during the treatment of berberine. It was found that the administration of berberine (20, 60 mg/kg; 30, 90 mg/kg) suppressed the expression of PKCε and TRPV1 which could be activated by hyperglycemia-induced inflammatory reaction. Our results also presented its capability to reduce the over expression of TNF-$\alpha$ in diabetic rats and mice. TNF-$\alpha$ is an inflammatory cytokine, which is closely related to diabetic peripheral neuropathy (DPN). Consequently, we supposed that berberine exerts its therapeutic effects in part by suppressing the inflammatory process and blocking the PKC pathway to inhibit TRPV1 activation, which damages neurons and causes diabetic pain.

Osteoporosis is a common disorder of bone remodeling, marked by excessive osteoclast formation. Recent studies indicated that berberine (BBR) is a potential natural drug for the treatment of various bone diseases. However, it still needs to be further studied for the treatment of osteoporosis. The current study investigated the inhibitory effects of BBR on receptor activator of nuclear factor-$\kappa$B ligand (RANKL)-induced osteoclast differentiation in vitro and in vivo. Cell-based assays were performed using osteoclasts generated in cultures of murine bone marrow-derived macrophages (BMMs) treated with RANKL and M-CSF. The effects of BBR on in vivo lipopolysaccharide (LPS)-mediated bone loss were evaluated using ICR mice. BBR significantly inhibited TRAP-positive osteoclast formation induced by RANKL. BBR also inhibited RANKL-induced Akt, p38 and ERK phosphorylation and I$\kappa$B degradation, and suppressed RANKL-induced expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1), which is a key transcription factors for osteoclast formation. BBR reduced the mRNA levels of osteoclast markers, including TRAP, osteoclast-associated receptor (OSCAR), cathepsin K, and ATPase H$+$ transporting V0 subunit d2 (ATP6v0d2). Moreover, BBR prevented LPS-mediated bone loss in vivo. We suggest BBR as a natural compound that can be a potential therapeutic agent for osteoclast-related bone diseases.

To systematically evaluate the efficacy and safety of berberine for the treatment of hyperlipidemia, six electronic literature databases including SinoMed, CNKI, WanFang Data, PubMed, Embase and The Cochrane Library were searched to collect clinical randomized controlled trials (RCTs) of berberine alone or combined with statins for the treatment of hyperlipidemia from the inception to 8 March 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included RCTs. Then, meta-analysis was performed by using RevMan 5.3 software. A total of 11 RCTs involving 1386 patients were finally included. The results of meta-analysis showed that compared with the placebo group, berberine could significantly reduce the total cholesterol and low-density lipoprotein levels and elevate the high density lipoprotein level ($P<0.05$). Compared with the simvastatin group, berberine was effective only in reducing the level of triglyceride ($\mathrm{\text{MD}}=-0.37$, 95% CI: $-$0.66, $-$0.07, $P=0.02$). There, however, was no statistical significance between the BBR group and simvastatin group in the low density lipoprotein and high density lipoprotein levels. Compared with the simvastatin group, berberine plus simvastatin was more effective in reducing the level of triglyceride ($\mathrm{\text{MD}}=-0.33$, 95% CI: $-$0.46, $-$0.20, $P<0.00001$) and total cholesterol ($\mathrm{\text{MD}}=-0.36$, 95% CI: $-$0.60, $-$0.12, $P=0.003$). In terms of adverse reactions, the incidence of adverse reactions including transaminase elevation and muscle aches was lower in the berberine alone or combined with simvastatin group than that in the control group, while the instance of constipation was higher. This study suggests that berberine is effective for hyperlipidemia. The quality and quantity of included studies, however, were dissatisfactory, which might decrease the reliability of the results. Higher quality studies are needed to provide more high quality evidence.

Critical care medicine is a medical specialty engaging the diagnosis and treatment of critically ill patients who have or are likely to have life-threatening organ failure. Sepsis, a life-threatening condition that arises when the body responds to infection, is currently the major cause of death in intensive care units (ICU). Although progress has been made in understanding the pathophysiology of sepsis, many drawbacks in sepsis treatment remains unresolved. For example, antimicrobial resistance, controversial of glucocorticoids use, prolonged duration of ICU care and the subsequent high cost of the treatment. Recent years have witnessed a growing trend of applying traditional Chinese medicine (TCM) in sepsis management. The TCM application emphasizes use of herbal formulation to balance immune responses to infection, which include clearing heat and toxin, promoting blood circulation and removing its stasis, enhancing gastrointestinal function, and strengthening body resistance. In this paper, we will provide an overview of the current status of Chinese herbal formulations, single herbs, and isolated compounds, as an add-on therapy to the standard Western treatment in the sepsis management. With the current trajectory of worldwide pandemic eruption of newly identified Coronavirus Disease-2019 (COVID-19), the adjuvant TCM therapy can be used in the ICU to treat critically ill patients infected with the novel coronavirus.

Rhizoma coptidis (Huang-lian) and Asian ginseng have been widely used in the treatment of diabetes and other concurrent diseases with apparent effects. This study investigated the effects of the active ingredients of R. coptidis and ginseng, berberine and ginsenoside Rb1, on depression-like behavior in a rat diabetes model. The animal model was established via a high-fat diet and intraperitoneal injection of streptozotocin, while the animal’s depression-like behavior was induced via chronic unpredictable mild stress. These experimental rats were divided into four groups: control, depression-like behavior (DLB), metformin plus fluoxetine hydrochloride (M+FH), and berberine plus ginsenoside Rb1 (B+GRb1) groups. Glucose metabolism and insulin resistance were evaluated by oral glucose test and glucose clamp study. Depression-like behavior was evaluated via behavioral analyses, including forced swim, sucrose preference, elevated plus maze, and open-field tests. HE and Nissl staining, plasma cortisol expression of adrenocorticotropic hormone, and brain-derived neurotrophic factor (BDNF) levels were assayed to explore the mechanisms of action. Compared with the control, rats in the DLB group had a significant increase in the levels of blood glucose and depression-like behavior. The B+GRb1 group significantly improved glucose metabolism and insulin resistance, reduced depression-like behavior, downregulated levels of plasma cortisol and adrenocorticotropic hormone under stress, and upregulated BDNF protein expression compared to the DLB rats. HE and Nissl staining data revealed that B+GRb1 protected neurons from pathological and morphological changes. Thus, berberine and ginsenoside Rb1 not only improved glucose metabolism in diabetic rats but also ameliorated their depression-like behavior under chronic unpredictable stress. Mechanistically, studied data with plasma hormonal levels and brain neuronal pathological/morphological changes supported the observed effects. The combination of berberine and ginsenoside Rb1 may have a clinical value in the management of diabetic patients with depression.

Berberine is an alkaloid from several medicinal plants originally used to treat diarrhea and dysentery as a traditional Chinese herbal medicine. In recent years, berberine has been discovered to exhibit a wide spectrum of biological activities in the treatment of diverse diseases ranging from cancer and neurological dysfunctions to metabolic disorders and heart diseases. This review article summarizes the clinical practice and laboratory exploration of berberine for the treatment of cardiometabolic and heart diseases, with a focus on the novel insights and recent advances of the underlying mechanisms recognized in the past decade. Berberine was found to display pleiotropic therapeutic effects against dyslipidemia, hyperglycemia, hypertension, arrhythmia, and heart failure. The mechanisms of berberine for the treatment of cardiometabolic disease involve combating inflammation and oxidative stress such as inhibiting proprotein convertase subtilisin/kexin 9 (PCSK9) activation, regulating electrical signals and ionic channels such as targeting human ether-a-go-go related gene (hERG) currents, promoting energy metabolism such as activating adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, modifying gut microbiota to promote transforming of berberine into its intestine-absorbable form, and interacting with non-coding RNAs via targeting multiple signaling pathways such as AMPK, mechanistic target of rapamycin (mTOR), etc. Collectively, berberine appears to be safe and well-tolerated in clinical practice, especially for those who are intolerant to statins. Knowledge from this field may pave the way for future development of more effective pharmaceutical approaches for managing cardiometabolic risk factors and preventing heart diseases.

Secondary metabolic disturbances in patients with schizophrenia or bipolar disorder may be attributed to olanzapine. It is important to prevent mild metabolic disorders progressing to metabolic syndrome. This study aims to investigate the effects of berberine on intestinal flora in patients with mild metabolic disorders induced by olanzapine. A total of 132 patients with schizophrenia, bipolar disorder, or schizoaffective psychosis that had been treated with olanzapine for at least 9 months were randomly assigned ($n$ = 66 each) to receive berberine or placebo tablets for 12 weeks. Metabolic assessments and intestinal flora were quantified at baseline and after 4, 8, and 12 weeks of treatment. Incidence rates of adverse reactions were recorded. FPG, FPI, HOMA-IR, HbA1, TG, BMI, and WC were significantly lower in patients who received berberine compared to placebo after 12 weeks of treatment ($P$< 0.05). The abundance of firmicutes and coliform were significantly lower and the abundance of bacteroides significantly higher in patients who received berberine compared to placebo after 12 weeks of treatment ($P$< 0.05). In patients who received berberine, the abundance of firmicutes was significantly decreased, and the abundance of bacteroides was significantly increased, and in patients who received placebo, the abundance of firmicutes was significantly increased post-treatment, compared to baseline (both $P$< 0.05). In conclusions, berberine may regulate intestinal flora and metabolism in patients with schizophrenia or bipolar disorder and mild metabolic disturbances induced by olanzapine.

Hyperuricemia (HUA) and its associated metabolic diseases seriously threaten human health, and commensal microbiota has been identified as one of the environmental triggers of HUA. The role of berberine (BBR) in the treatment of HUA has begun to receive attention in recent years. However, how BBR modulates the microbiota to slow HUA progression is unclear. In this study, we showed that BBR alleviated potassium oxonate (PO)-induced HUA in mice by suppressing the expression of xanthine oxidase (XOD) in the liver and urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) in the kidney. The BBR also improved renal inflammation by inhibiting the expression of TNF-$\alpha$, IL-1$\beta$, and caspase-1. Subsequently, we evaluated whether the observed anti-HUA effects of BBR were associated with changes in gut microbial structure in mice. 16S rRNA sequencing data showed that BBR significantly altered the community compositional structure of the gut microbiota. Specifically, BBR enriched the abundance of Coprococcus, Bacteroides, Akkermansia, and Prevotella. Antibiotic treatment can reverse the anti-HUA effects of BBR that further supports the role of the gut microbiota. In conclusion, our study provides evidence that BBR ameliorates PO-induced HUA by modulating the gut microbiota.

Breast cancer is a malignant disease with an increasing incidence. Chemotherapy is still an important means for breast cancer treatment, but multidrug resistance (MDR) greatly limits its clinical application. Therefore, the high-efficiency MDR reversal agents are urgently needed. Traditional Chinese medicine (TCM) monomers have unique advantages in reversing chemotherapeutic MDR because of its low toxicity, high efficiency, and ability to impact multiple targets. This review firstly summarizes the major mechanisms of MDR in breast cancer, including the reduced accumulation of intracellular chemotherapeutic drugs, the promoted inactivation of intracellular chemotherapeutic drugs, and the enhanced damage repair ability of DNA, etc., and secondly highlights the research progress of 15 kinds of TCM monomers, including curcumin, resveratrol, emodin, apigenin, tetrandrine, gambogic acid, matrine, paeonol, schisandrin B, $\beta$-elemene, astragaloside IV, berberine, puerarin, tanshinone IIA, and quercetin, in reversing MDR of breast cancer. This review also provides the suggestion for the future research of MDR reversal agents in breast cancer.

Coptis chinensis Franch (RC), has historically been used for the treatment of “Xiao Ke” and “Xia Li” symptoms in China. “Xia Li” is characterized by abdominal pain and diarrhea, which are similar to the clinical symptoms of ulcerative colitis (UC). For the first time, this study aims to compare the anti-colitis effects of berberine (BBR) and total RC alkaloids (TRCA) and investigate the underlying metabolites and gut microbiota biomarkers. Metabolomics results showed that several colitis-related biomarkers, including lysophosphatidyl ethanolamine, lysophosphatidylcholine, scopolamine-methyl-bromide, N1-methyl-2-pyridone-5-carboxamide, 4-hydroxyretinoic acid, and malic acid, were significantly improved in model mice after BBR and TRCA treatments. High-dose BBR and TRCA treatments reversed the mouse colon shortening caused by dextran sodium sulfate (DSS), alleviated bowel wall swelling, and reduced inflammatory cell infiltration. BBR and TRCA restored the damaged mucosa integrity in colitis mice by upregulating claudin 1 and occludin, preventing colon epithelium apoptosis by inhibiting the cleavage of caspase 3. Additionally, BBR and TRCA significantly decreased the richness of the pathogenic bacteria Bacteroides acidifaciens but increased the abundance of the probiotic Lactobacillus spp. Notably, TRCA exhibited superior anti-colitis effects to those of BBR. Thus, this agent warrants further study and application in the treatment of inflammatory bowel disease in the clinic.