Pharmacokinetics and tissue distribution of 12 major active components in normal and chronic gastritis rats after oral administration of Weikangling capsules.

ETHNOPHARMACOLOGICAL RELEVANCE: Weikangling Capsules (WKLCs) have been used in the clinic for the treatment of gastrointestinal disorders for more than 30 years. However, the pharmacokinetic characteristics and tissue distribution of its major bioactive components in rats under different physiological and pathological conditions are unclear. AIM OF THE STUDY: In this study, we aimed to clarify the differences in pharmacokinetic parameters and tissue distribution of the major active components in WKLCs under physiological and pathological states. MATERIALS AND METHOD: Normal and ethanol-induced chronic gastritis rats received 2.16 g/kg WKLCs by gavage, and urine, feces, plasma, and tissue (heart, liver, spleen, lung, kidney, stomach, and small intestine) samples were obtained. The active components in urine, feces and plasma were detected by ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). A rapid and sensitive analytical method, ultra-high-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (UHPLC-QTRAP-MS/MS), was established and validated to clarify and compare the pharmacokinetics and tissue distribution of the major active components in normal and chronic gastritis rats. RESULTS: A total of 36 chemical components in the feces, urine, and plasma of chronic gastritis rats were identified by UHPLC-Q-TOF-MS/MS. Among them, 20 were the prototype components of WKLCs, and 16 were metabolites. The pharmacokinetic characteristics and tissue distribution of 12 prototype components were successfully analyzed by UHPLC-QTRAP-MS/MS. The pharmacokinetic results showed that the Cmax, AUC0-t, and AUC0-∞ of paeoniflorin, glycyrrhizic acid, and glycyrrhetinic acid were distinctly higher than those of the other components in normal and chronic gastritis rats. Compared to normal rats, the Cmax, AUC0-t, and AUC0-∞ of albiflorin, liquiritin apioside, liquiritin, isoliquiritin, ononin, isoliquiritigenin, dactylorhin A, and glycyrrhizic acid were significantly increased in chronic gastritis rats (P < 0.05), while the Cmax, AUC0-t and AUC0-∞ of militarine and liquiritigenin had significantly lower decreases in chronic gastritis rats (P < 0.05). The results of the tissue distribution showed that the 12 components were widely distributed in the heart, liver, spleen, lung, kidney, stomach, and small intestine of rats, of which the liver, kidney, stomach, and small intestine were the main accumulative organs. Compared with normal rats, the concentrations of 12 components in the liver, kidney, stomach, and small intestine of chronic gastritis rats were widely higher than those of normal rats at the same time points. CONCLUSION: The pharmacokinetic characteristics and tissue distribution of 12 active components of WKLCs were comprehensively characterized and elucidated in normal and chronic gastritis rats. These findings laid a solid foundation for revealing the pharmacodynamic material basis of WKLCs in treating gastrointestinal disorders.

Weikangling capsules combined with omeprazole ameliorates ethanol-induced chronic gastritis by regulating gut microbiota and EGF-EGFR-ERK pathway.

AIMS: Weikangling capsules (WKLCs) have been widely used in the treatment of chronic gastritis. Whether used alone or combined with omeprazole (OME), it shows a significant effect. However, the mechanisms haven't been established. The study aimed to explore the mechanisms of WKLCs and its combination with OME on chronic gastritis. MAIN METHODS: The components of WKLCs and EA (the ethyl acetate extraction extracted from WKLCs) fraction were analyzed. Then chronic gastritis model rats were induced by 56 % ethanol and treated with OME, low dose of WKLCs (WKL), high dose of WKLCs (WKH), WKLCs combined with OME (WO), and EA fraction (EA) to evaluate the mechanisms of WKLCs, drug combination and EA fraction. KEY FINDINGS: A total of 22 components of WKLCs were quantified, among them 18 were enriched in EA fraction. WKLCs alleviated the morphology and inflammation of gastric mucosa and downregulated the levels of inflammatory factors (IL-1ß, TNF-α, IL-6) and epidermal growth factor (EGF) in serum by inhibiting the EGF-EGFR-ERK pathway, regulating gut microbiota composition and SCFAs contents in feces. WKLCs plus OME was better than OME. EA fraction improved digestive function by increasing pepsin activity and decreasing gastrointestinal hormones (GAS and VIP) compared with WKLCs. SIGNIFICANCE: This study elucidated that the effect of WKLCs and its combination with OME in the treatment of chronic gastritis was attributed to regulating the composition of the gut microbiota and inhibiting the EGF-EGFR-ERK pathway. The EA fraction is an inseparable effective substance of WKLCs. This study provides scientific evidence for clinical application.

A multi-evaluating strategy for Weikangling capsules: Chemical profiling, fingerprinting combined with quantitative analysis, quantity transfer, and dissolution curve.

Weikangling capsules (WKLCs), a Chinese patent medicine consisting of 8 Chinese drugs, have been widely used in clinic to treat gastrointestinal diseases for more than 30 years. The current "Chinese Pharmacopoeia" (2020 Edition, ChP2020) uses paeoniflorin content (≥ 1.0 mg per capsule) as the standard of quality control, but it is insufficient to evaluate the overall quality of WKLCs. An efficient and economic method for quality control is urgently needed to ensure the quality consistency and clinical effects of WKLCs. Herein, a systematic and reliable method for the rapid analysis of chemical components in WKLCs was established for the first time based on ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). A total of 115 components covering 7 herbs in WKLCs were preliminarily identified by comparison with standard substances or literature. To evaluate the quality of 26 batches of WKLCs, a new method of fingerprinting combined with quantitative analysis was established, and 16 common peaks were selected to establish the fingerprint similarity model (similarity>0.90). Simultaneously, the contents of albiflorin, paeoniflorin, dactylorhin A, militarine, and glycyrrhizic acid were determined to be 0.82 ± 0.22, 2.09 ± 0.24, 1.15 ± 0.40, 3.73 ± 0.76 and 0.99 ± 0.20 mg/capsule, respectively. The transfer rates and dissolution curves of the five compounds were successfully detected in WKLCs, and the average transfer rates were 67.2%, 33.0%, 68.3%, 54.7%, and 33.7%, respectively. Notably, the dissolution profiles of different manufacturers presented remarkable differences in pH 1.2 hydrochloric acid solution. This method not only qualitatively identified the chemical components of Chinese patent medicines at the microlevel but also evaluated the quality consistency between batches at the macrolevel, which provided a comprehensive reference for the quality consistency of Chinese patent medicines between batches.

Clinical contrast study of Weikangling and Weifuchun for chronic atrophic gastritis and precancerous lesions / 药物评价研究

Objective To explore the clinical effect of Weikangling and Weifuchun treatment of chronic atrophic gastritis and precancerous lesions.Methods 85 cases of CAG precancerous lesions treated in our hospital from Jan.2012 to Dec.2016 were selected as the research object,and were randomly divided into control group (n =41) and study group (n =44).The control group were given Weifuchun,and the study group were given Wei Kangling.The pathological score and clinical efficacy were compared between the two groups before and after treatment.Results After treatment,inflammation,atrophy,intestinal metaplasia scores of the two groups were significantly decreased than before treatment in addition to dysplasia (P ＜ 0.05),and inflammation and intestinal metaplasia in the study group were significantly lower than those in the control group (P ＜ 0.05).The total effective rate of the study group was 90.91％,which was higher than75.61％ of the control group (P ＜ 0.05).Conclusions The effect of Wei Kangling in treating precancerous lesions of CAG is significant,especially for the histological changes of inflammation and intestinal metaplasia.

Clinical contrast study of Weikangling and Weifuchun for chronic atrophic gastritis and precancerous lesions / 药物评价研究

Objective To explore the clinical effect of Weikangling and Weifuchun treatment of chronic atrophic gastritis and precancerous lesions.Methods 85 cases of CAG precancerous lesions treated in our hospital from Jan.2012 to Dec.2016 were selected as the research object,and were randomly divided into control group (n =41) and study group (n =44).The control group were given Weifuchun,and the study group were given Wei Kangling.The pathological score and clinical efficacy were compared between the two groups before and after treatment.Results After treatment,inflammation,atrophy,intestinal metaplasia scores of the two groups were significantly decreased than before treatment in addition to dysplasia (P ＜ 0.05),and inflammation and intestinal metaplasia in the study group were significantly lower than those in the control group (P ＜ 0.05).The total effective rate of the study group was 90.91％,which was higher than75.61％ of the control group (P ＜ 0.05).Conclusions The effect of Wei Kangling in treating precancerous lesions of CAG is significant,especially for the histological changes of inflammation and intestinal metaplasia.