Author: Zhang, Jun-Feng ; Cheng, Yu-Qin ; Ma, Wen-Shuo ; Wu, Jian-Ping ; Meng, Yu-Fen ; Zhang, Jun-feng ; Meng, Yu-fen ; Xiao, Ling ; Shi, Li-yun ; Ma, Wen-shuo ; Zhang, Wei ; Shi, Li-Yun ; Zhu, Wen-fei ; Cheng, Chun ; Chen, Lei ; Wu, Jian-ping ; Cheng, Yu-qin ; Zhu, Wen-Fei

BACKGROUNDGastric intestinal metaplasia (GIM) is a crucial stage in the progression of gastric cancer. Huangqi Jianzhong decoction (HQJZ) has emerged as a leading therapeutic strategy for treating GIM patients with cold intolerance in traditional Chinese medicine clinics, but the detailed mechanism remains poorly understood.OBJECTIVEThe present study aimed to elucidate the molecular mechanism by which HQJZ alleviates GIM in a rat model on the basis of the gut microbiota‒thyroid axis.METHODSA GIM rat model was established by administering cold salicylic acid and sodium deoxycholate (SDC) for 12 weeks, followed by gavage treatment with HQJZ for an additional four weeks. Lianpu Yin (LPY) was used as a comparison formula. The cold tolerance characteristics of GIM rats were evaluated using cold tolerance and temperature‒tropism experiment experiments. Thyroid pathological changes were evaluated with HE staining, and thyroid function was measured via quantification of T3 and T4 levels with ELISA. The gut microbiota was analyzed using 16S rRNA gene sequencing, and fecal butyric acid and serum metabolites were quantified utilizing metabolomics. The key molecular mechanism was verified in the Nthy-ori 3-1 cell model.RESULTSHQJZ, but not LPY, significantly improved gastric mucosa and thyroid tissue lesions in GIM rats, increased the serum levels of the thyroid hormones T3 and T4, and enhanced cold tolerance. HQJZ treatment promoted the enrichment of fecal butyrate-producing bacteria, specifically the bacteria Allobaculum and Bifidobacterium, resulting in a marked increase in fecal butyric acid concentrations. HQJZ treatment significantly diminished the levels of mitochondrial damage-related serum metabolites, including p-cresol sulfate and indoxyl sulfate. Mechanistically, in vivo investigations further demonstrated that butyric acid not only improved thyroid tissue lesions but also restored the fecal microbiota structure, as well as low-temperature tropism, in GIM rats. Furthermore, butyrate diminished the mitochondrial damage induced by SDC in these cells, as evidenced by decreased reactive oxygen species levels and increased ATP production and mitochondrial membrane potential. Importantly, in vitro studies revealed that butyrate protected against SDC-induced injury in Nthy-ori 3-1 cells through the upregulation of TG, TPO, and TSHR expression.CONCLUSIONSHQJZ promotes cold tolerance and improves thyroid function in GIM rats by enriching gut butyrate-producing bacteria.

01 May 2024·Journal of Pharmaceutical and Biomedical Analysis

Exploration of the intestinal flora to reveal the important contribution of Radix Astragali to Huangqi Jianzhong Tang in treating chronic atrophic gastritis rats

Article

Author: Zhang, Ruonan ; Qin, Xuemei ; Liu, Yuetao

Radix Astragali (Huangqi in Chinese, HQ) is a commonly used Chinese herbal medicine for thousands of years. In this study, A classic prescription Huangqi Jianzhong tang (HQJZ) was selected to evaluate the important effect of HQ on rats with chronic atrophic gastritis (CAG) from the perspective of intestinal flora in cecal contents samples. Traditional pharmacological indicators, including weight change, pathological examination and biochemical indicators showed that HQ exerted favorable contribution to HQJZ against CAG, where the efficiencies of HQ and HQJZ were better than HY (HQJZ prepared without HQ). An accurate strategy was adopted to screen out the differential metabolites in the metabolomis analysis of intestinal flora in cecal contents samples based on the optimal screening factors, including VIP (importance of variables in projection), FC (fold change), AUROC (area under the receiver operating characteristic curve) and -ln(p-value), which were evaluated based on their interpreting, grouping, and predicting abilities of the performed orthogonal partial least-squares-discriminate analysis (OPLS-DA) models. Ten altered differential metabolites were obtained and associated with the intestinal flora, which HQ exerted the important metabolic contributions to HQJZ. The efficacy on the diversity of intestinal flora and their correlations with the altered metabolites further showed the important role of HQ in HQJZ composition. This work provided valuable approach for looking for potential biomarkers associated with metabolomics research with more accuracy, and provided new insights into the mechanisms to explain the efficacy of HQ contributing to HQJZ formula.

01 Nov 2023·Biomedical chromatography : BMC

Huangqi Jianzhong Tang treats chronic atrophic gastritis rats by regulating intestinal flora and conjugated bile acid metabolism.

Article

Author: Huang, Xingyue ; Liu, Yuetao ; Zhang, Hui ; Wang, Guohong

Huangqi Jianzhong Tang (HQJZ) is effective for treating chronic atrophic gastritis (CAG). The present study was carried out to reveal the mechanism of HQJZ in CAG rats. The metabolism and microbial composition of the cecal contents in CAG rats were analyzed through the integration of an untargeted metabolomic approach using ultra-high-performance liquid chromatography coupled with the quadrupole-time of flight mass spectrometry (UHPLC-QTOF-MS) and 16S rRNA gene sequencing, respectively. Finally, MetOrigin analyses were performed to explore the relationship between differential metabolites and intestinal flora. The results showed that HQJZ could significantly regulate metabolic disorders, especially conjugated acid metabolites. 16S rRNA gene sequencing analysis illustrated that HQJZ decreased the abundance of Acetobacter, Desulfovibrio, Escherichia, and Shigella. MetOrigin metabolite traceability analysis showed that the six bile acids associated with HQJZ efficacy included three bacteria-host cometabolites, which were involved in the primary bile acid biosynthesis pathway. Research presented here confirmed that conjugated bile acid metabolism was key to the treatment of CAG by HQJZ and correlates strongly with Bacteroides acidifaciens and Prevotella copri. These findings provide new insights into the mechanisms to explain the efficacy of HQJZ.

100 Deals associated with Huangqi Jianzhong Decoction

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Indication	Country/Location	Organization	Date
Asthenia	JP	Toyo-yakuko Co., Ltd	01 Oct 1986
Sleep Initiation and Maintenance Disorders	JP	Toyo-yakuko Co., Ltd	01 Oct 1986

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