JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2021
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IF 3.935
Yan-Ting Fan,Ping Zhong,Jin-Di Xu,Shan-Shan Zhou,Ming Kong,Gui-Rong Zhou,Qian Mao,Song-Lin Li
Chang-Kang-Fang formula (CKF), a multi-herbs traditional Chinese medicine (TCM) prescription for treating irritable bowel syndrome (IBS), has been clinically applied in the traditional form of mixed-herb decoction (MHD), or in the modern form of combined single-herb decoction (cSHD, so called dispensing granule decoction) in the near decades, but the chemical consistency between the MHD and cSHD is still unknown. Herein, a new strategy by integrating multiple-chromatographic approaches to characterize both polysaccharides and small molecules was developed to compare the chemical consistency between MHD and cSHD. Sixteen small molecules were simultaneously qualified and quantified by UPLC-QTOF-MS/MS, the molecular weight distribution of polysaccharides was characterized by HPGPC-ELSD, while the monosaccharide composition and total saccharides content were determined by HPLC-PDA and UV-VIS, respectively. It was found that the molecular weight range and monosaccharide composition of polysaccharides, as well as the composition of small molecules, were identical between MHD and cSHD. However, the contents of berberine, epiberberine, coptisine, palmatine, albiflorin and paeoniflorin in MHD were significantly lower than those in cSHD, whereas the content of polysaccharides in MHD was higher than that in cSHD, indicating that there is a significant difference in the quality between MHD and cSHD, in particular for the relative contents of major small molecules and polysaccharides. Whether or not these quality variations affect the efficacy and safety of CKF deserves further investigation.
研究领域:
中药学
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色谱分析
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药物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Sihao Zhang,Danmei Tian,Zixuan Xia,Fengge Yang,Yanhui Chen,Zhihong Yao,Yi He,Xinglong Miao,Guirong Zhou,Xinsheng Yao,Jinshan Tang
Ethnopharmacological relevance Chang-Kang-Fang (CKF), originated from traditional Chinese medicine (TCM) formulas, has been utilized to treat diarrhea predominant irritable bowel syndrome (IBS-D) based on clinical experience. However, the underlying mechanism of CKF for treating IBS-D remains unclear and need further clarification. Aim of the study The objective of this present investigation was to validate the efficacy of CKF on IBS-D model rats and to uncover its potential mechanism for the treatment of IBS-D. Materials and Methods We first established the IBS-D rat model through neonatal maternal separation (NMS) in combination with restraint stress (RS) and the administration of senna decoction via gavage. To confirm the therapeutic effect of CKF on treating IBS-D, abdominal withdrawal reflex (AWR) scores, the quantity of fecal pellets, and the fecal water content (FWC) were measured to evaluate the influence of CKF on visceral hypersensitivity and the severity of diarrhea symptom after the intragastric administration of CKF for 14 days. Subsequently, enzyme linked immunosorbent assay (ELISA) was applied to assess the effect of CKF on neuropeptides substance P (SP) and 5-hydroxytryptamine (5-HT), as well as inflammatory cytokines in serum and in intestinal tissues. Further, colonic pathological changes, the amount of colonic mast cells, and the expression level of occludin in rat colon tissues, were investigated by hematoxylin-eosin (HE) staining, toluidine blue staining, and immunohistochemistry, respectively. To explore the underlying mechanisms, alterations in colonic RNA transcriptomics for the normal, model, and CKF treatment groups were assessed using RNA sequencing (RNA-Seq). Subsequently, quantitative real-time polymerase chain reaction (qRT-PCR), western blot (WB), and immunofluorescence (IF) assays were applied to validate the effect of CKF on predicted pathways in vivo and in vitro . In addition, to elucidate the potential active compounds in CKF, 11 representative components found in CKF were selected, and their anti-inflammation potentials were evaluated using LPS-treated RAW264.7 cell models. Results CKF treatment significantly reduced the number of fecal pellets, attenuated visceral hypersensitivity, and decreased 5-HT and SP concentrations in serum and colon tissues, along with a reduction in colonic mast cell counts, correlating with improved symptoms in IBS-D rats. Meanwhile, CKF treatment reduced the colonic inflammatory cell infiltration, lowered the levels of IL-6, TNF- α , and IL-1 β in serum and colon tissues, and increased the occludin protein expression in colon tissues to improve inflammatory response and colonic barrier function. RNA-Seq, in conjugation with our previous network pharmacology analysis, indicated that CKF might mitigate the symptoms of IBS-D rats by inhibiting the Toll like receptor 4/Nuclear factor kappa-B/NLR family pyrin domain-containing protein 3 (TLR4/NF- κ B/NLRP3) pathway, which was confirmed by WB, IF, and qRT-PCR experiments in vivo and in vitro . Furthermore, coptisine, berberine, hyperoside, epicatechin, and gallic acid present in CKF emerged as potential active components for treating IBS-D, as they demonstrated in vitro anti-inflammatory effects. Conclusion Our findings demonstrate that CKF effectively improves the symptoms of IBS-D rats, potentially through the inhibition of the TLR4/NF- κ B/NLRP3 pathway. Moreover, this study unveils the potential bioactive components in CKF that could be applied in the treatment of IBS-D.
研究领域:
药理学
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胃肠病学
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传统中药
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2026
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IF 11.3
Fengge Yang,Danmei Tian,Yuting Zhang,Zixuan Xia,Yunjuan Li,Xinsheng Yao,Yanxia Xiong,Guirong Zhou,Hongwei Liu,Jinshan Tang
CKF ameliorates intestinal dysfunction and neurobehavioral abnormalities in IBS-D mice. • CKF boosts L. johnsonii and tryptophan-derived indoles, notably ILA. • L. johnsonii acts as a psychobiotic for IBS-D and comorbidities. • ILA improves IBS-D intestinal and behavioral deficits mainly via AhR activation. • CKF targets the L. johnsonii -ILA-AhR/IL-22 gut-brain axis. Background Gut dysbiosis contributes to irritable bowel syndrome (IBS) by disrupting intestinal barrier functions and promoting inflammation. Chang‑kang‑fang (CKF), a Chinese herbal formula proven effective for diarrhea‑predominant IBS (IBS‑D) in a phase III trial, is thought to modulate the gut microbiota, yet the underlying mechanism remains unclear. Purpose To elucidate how CKF ameliorates IBS‑D by modulating the gut microbiota. Methods IBS‑D was induced by restraint stress, tail pinch, and senna gavage. Intestinal function, inflammation, and behavior were evaluated. Gut microbiota and metabolites were profiled via 16S rRNA sequencing and metabolomics. FMT confirmed the causal involvement of the microbiota. The key microbe and metabolite were validated in vivo . Mechanistic analyses evaluated intestinal barrier integrity, systemic inflammation, hippocampal blood‑brain barrier (BBB) function, neuroinflammation, and synaptic plasticity. Results CKF alleviated diarrhea, visceral hypersensitivity, inflammation, barrier dysfunction, and anxiety‑ and depression‑like behaviors. These benefits were associated with gut microbiota remodeling, featuring enrichment of Lactobacillus johnsonii and enhanced tryptophan metabolism. FMT confirmed that this microbial remodeling mediates the therapeutic effects of CKF. Supplementation with L. johnsonii or its metabolite indole‑3‑lactic acid (ILA) largely recapitulated these gut-brain benefits via AhR/IL‑22 activation. Mechanistically, CKF‑induced L. johnsonii enrichment activated the ILA-AhR-IL‑22 pathway, which enhanced intestinal and BBB integrity, thereby attenuating systemic and neuroinflammation, and restoring hippocampal synaptic plasticity. Conclusion This study positions CKF as a microbiota‑modulating therapy for IBS‑D that restores gut‑brain homeostasis via the L. johnsonii -ILA-AhR-IL‑22 axis, highlighting L. johnsonii and ILA as potential therapeutics for IBS and its comorbidities. Download: Download high-res image (278KB) Download: Download full-size image Chang-Kang-Fang alleviates IBS-D and comorbid depression by activating the Lactobacillus johnsonii -indole-3-lactic acid-aryl hydrocarbon receptor/interleukin-22 gut-brain axis.
✓ 已验证
DOI
高影响因子
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