The effect and mechanism of Jiao-tai-wan in the treatment of diabetes mellitus with depression based on network pharmacology and experimental analysis

Abstract

Background The incidence of diabetes mellitus (DM) and depression is increasing year by year around the world, bringing a serious burden to patients and their families. Jiao-tai-wan (JTW), a well-known traditional Chinese medicine (TCM), has been approved to have hypoglycemic and antidepressant effects, respectively, but whether JTW has such dual effects and its potential mechanisms is still unknown. This study is to evaluate the dual therapeutic effects of JTW on chronic restraint stress (CRS)-induced DM combined with depression mice, and to explore the underlying mechanisms through network pharmacology. Methods CRS was used on db/db mice for 21 days to induce depression-like behaviors, so as to obtain the DM combined with depression mouse model. Mice were treated with 0.9% saline (0.1 ml/10 g), JTW (3.2 mg/kg) and Fluoxetine (2.0 mg/kg), respectively. The effect of JTW was accessed by measuring fasting blood glucose (FBG) levels, conducting behavioral tests and observing histopathological change. The ELISA assay was used to evaluate the levels of inflammatory cytokines and the UHPLC-MS/MS method was used to determine the depression-related neurotransmitters levels in serum. The mechanism exploration of JTW against DM and depression were performed via a network pharmacological method. Results The results of blood glucose measurement showed that JTW has a therapeutic effect on db/db mice. Behavioral tests and the levels of depression-related neurotransmitters proved that JTW can effectively ameliorate depression-like symptoms in mice induced by CRS. In addition, JTW can also improve the inflammatory state and reduce the number of apoptotic cells in the hippocampus. According to network pharmacology, 28 active compounds and 484 corresponding targets of JTW, 1407 DM targets and 1842 depression targets were collected by screening the databases, and a total of 117 targets were obtained after taking the intersection. JTW plays a role in reducing blood glucose level and antidepressant mainly through active compounds such as quercetin, styrene, cinnamic acid, ethyl cinnamate, (R)-Canadine, palmatine and berberine, etc., the key targets of its therapeutic effect include INS, AKT1, IL-6, VEGF-A, TNF and so on, mainly involved in HIF-1 signal pathway, pathways in cancer, Hepatitis B, TNF signal pathway, PI3K-Akt signal pathway and MAPK signaling pathway, etc. Conclusion Our experimental study showed that JTW has hypoglycemic and antidepressant effects. The possible mechanism was explored by network pharmacology, reflecting the characteristics of multi-component, multi-target and multi-pathway, which provides a theoretical basis for the experimental research and clinical application of JTW in the future.

Combination of Shengmai San and Radix puerariae ameliorates depression‐like symptoms in diabetic rats at the nexus of PI3K/BDNF/SYN protein expression

“…The cure is directed to reduce depression in individuals with diabetes to help them socialize, thus improving their health status. TCMs have been reported to cure many ailments, including diabetes‐associated depressive symptoms 39,40 …”

“…TCMs have been reported to cure many ailments, including diabetes-associated depressive symptoms. 39,40 Thus, this study was designed to formulate R-SMS that comprises four bioactive components, namely Puerarin, Ginsenosides, Schizandrin, and Ruscogenin. 41 All the components of R-SMS have been shown to be neuroprotective, especially antidepressant activity among chronic unpredictable mild stress mouse models.…”

“…Several TCM formulations, decoction of Pinellia and Magnolia bark, and Chinese Angelica decoction have been used for replenishing blood, lowering glucose level, and relieving depression. Furthermore, decoction for tonifying the kidney‐yin has shown to improve depression comorbidities in diabetes 39,40 . Recently, our group has shown that a combination of Shengmai San and Radix puerariae (R‐SMS) significantly improves learning and memory deficit in diabetic rats 41 .…”

“…Furthermore, decoction for tonifying the kidney-yin has shown to improve depression comorbidities in diabetes. 39,40 Recently, our group has shown that a combination of Shengmai San and Radix puerariae (R-SMS) significantly improves learning and memory deficit in diabetic rats. 41 Therefore, this study was designed to explore the curative potential of R-SMS to reverse diabetes-associated depressive disorder in streptozotocin (STZ) rats and to elucidate its molecular mechanism at the nexus of PI3K/ BDNF/SYN expression.…”

Effects of the ApoE genotype on cognitive function in aging mice fed with a high-fat diet and the protective potential of n-3 polyunsaturated fatty acids

“…10 The insulin receptor substrate 1/phosphoinositide 3-kinase/protein kinase B insulin receptor substrate 1/glucose transporter type 4 (IRS-1/PI3K/AKT/GLUT4) signaling pathway is a crucial downstream molecular pathway of insulin, governing glucose metabolism, IR, and neuronal survival. 11,12 Notably, studies have indicated that ApoE4 can impair cerebral insulin signaling compared to ApoE3, resulting in reduced responsiveness to both peripheral and cerebral insulin signaling upon insulin administration. 13 Hence, examining alterations in the insulin signaling pathway can provide valuable insights into the impact of interventions on the IR status and brain function in the context of the ApoE genotype.…”