Guangdong Province Research Centre for Chinese Integrative Medicine Against Metabolic Disease, Guangdong TCM key laboratory against metabolic diseases, Key Unit of Modulating Liver to Treat Hyperlipemia SATCM, The Institute of Chinese Medicinal Sciences, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Centre, Guangzhou 510006, China.
Biomed Pharmacother. 2020 Jan;121:109421. doi: 10.1016/j.biopha.2019.109421. Epub 2019 Nov 25.
BACKGROUND/AIMS: Fufang Zhenzhu Tiao Zhi (FTZ) capsule is a Chinese herbal preparation under the guidance of professor Guo Jiao's new theory of "Tiaogan Qishu Huazhuo" for disorders of glucose and lipid metabolism for more than twenty yares, which has been demonstrated to exhibit potential anti-aging effects such as regulation of glucose and lipid metabolisms and antiinflammatory and antioxidative effects. This study attempts to reveal the anti-intestinal aging effect and possible mechanism of FTZ.
The mice were divided into three groups: the control group, model group and treatment group. The treatment group was given 1.0 g/kg body weight of FTZ extract administered by oral gavage once a day for 12 consecutive weeks. Age-related alterations such as HE staining of intestinal tissue morphology, mRNA levels of intestinal telomerase and inflammatory cytokines were observed Fecal samples were used for ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) and 16S rRNA gene sequencing analyses to reveal age-related metabolic perturbations and gut flora disorders to demonstrate the effects of FTZ.
Emerged pathological morphology of intestinal tissues, upregulated relative expression level of gut inflammatory factors and decreased relative expression level of telomerase mRNA in aging mice illustrated characteristic senescent phenotypes in model group. FTZ treatment significantly lowered intestinal inflammation levels, enhanced telomerase activity, partially reversed the fecal metabolites abnormalities and restored the disorders of intestinal flora. Multiple potential metabolites were associated with linoleic acid, glycerophospholipid, α-linolenic acid, biosynthesis of unsaturated fatty acids and glycerolipid metabolisms. Several decreased beneficial butyrate-producing bacteria like S24-7, possible Alkaliphilus belonging to the Clostridia class and increased harmful bacteria such as potentially toxic metabolite hydrogen sulfide-producer Bilophila and Desulfovibrio, inflammation-mediator Mucispirillum were determined in present aging mice. These age-related poor alterations could be partially attenuated by FTZ treatment.
The pathologic changes of intestinal senescence and the decrease of telomerase mRNA in elderly mice was observed. FTZ may sever as a novel delaying intestinal aging strategy via three pathways for anti-inflammatory, improving gut metabolites and gut flora. This study not only provided biological basis for the theory of treating different diseases with the same treatment in TCM, but also provided objective evidence for incorporating aging into the system of"glucose-lipid metabolism disease".
背景/目的：复方珍珠调脂胶囊是在郭姣教授“调肝启枢化浊”新理论指导下，经过二十多年的研究，开发的一种治疗糖脂代谢紊乱的中药复方制剂，具有调节糖脂代谢、抗炎、抗氧化等潜在的抗衰老作用。本研究试图揭示 FTZ 的抗肠道衰老作用及其可能的机制。
将小鼠分为三组：对照组、模型组和治疗组。治疗组给予 1.0 g/kg 体重的 FTZ 提取物，每天口服一次，连续 12 周。观察肠道组织形态的 HE 染色、肠道端粒酶和炎症细胞因子的 mRNA 水平等与年龄相关的改变。采用超高效液相色谱-四极杆飞行时间质谱（UPLC-QTOF/MS）和 16S rRNA 基因测序分析粪便样本，揭示与年龄相关的代谢紊乱和肠道菌群失调，以证明 FTZ 的作用。
衰老模型组小鼠肠道组织出现病理形态改变，肠道炎症因子相对表达水平上调，端粒酶 mRNA 相对表达水平下调，呈现典型的衰老表型。FTZ 治疗可显著降低肠道炎症水平，增强端粒酶活性，部分逆转粪便代谢物异常，恢复肠道菌群紊乱。多个潜在代谢物与亚油酸、甘油磷脂、α-亚麻酸、不饱和脂肪酸的生物合成和甘油脂代谢有关。本研究中发现一些有益的丁酸产生菌如 S24-7、可能属于梭菌纲的 Alkaliphilus 以及有害的细菌如潜在有毒代谢物硫化氢产生菌 Bilophila 和脱硫弧菌、炎症介质 Mucispirillum 减少，这些与年龄相关的不良改变可部分被 FTZ 治疗减轻。
观察到老年小鼠肠道衰老的病理变化和端粒酶 mRNA 的减少。FTZ 可能通过抗炎、改善肠道代谢物和肠道菌群三条途径成为一种新的延缓肠道衰老的策略。本研究不仅为中医“同病异治”理论提供了生物学依据，也为将衰老纳入“糖脂代谢病”体系提供了客观依据。
