Diabetes mellitus (DM) is a global health issue in the twenty-first century, and there are numerous challenges in preventing and alleviating its chronic complications. The herb Epimedium has beneficial therapeutic effects on various human diseases, including DM. Its major flavonoid component, icariin, has significant anti-DM activity and may help improve pancreatic β-cell dysfunction and insulin resistance. Furthermore, preclinical evidence has shown that icariin and its in vivo bioactive form, icariside II, have preventive and therapeutic effects on several diabetic complications, including diabetic cardiomyopathy, diabetic vascular endothelial disorder, diabetic nephropathy, and diabetic erectile dysfunction. In this review, we present the general and toxicological information concerning icariin and icariside II and review the anti-DM effects of icariin from a molecular perspective. Additionally, we discuss the potential benefits of icariin and icariside II on the important pathological mechanisms of various diabetic complications. Despite positive preclinical evidence, additional investigations are needed before relevant clinical studies can be conducted. Therefore, we conclude with suggestions for future research. Hopefully, this review will provide a comprehensive molecular perspective for future research and product development related to icariin and icariside II in treating DM and diabetic complications.

Diabetes mellitus (DM) is a metabolic disease caused by multiple factors such as genetics, environment, and lifestyle. Bisphenol A (BPA), as one of the most common endocrine-disrupting chemicals (EDCs), has been strongly implicated in the development of type 2 diabetes mellitus (T2DM). BPA exposure is associated with target organ damage in DM and may exacerbate the progression of some chronic complications of DM. This paper reviews relevant epidemiological, in vivo, and in vitro studies to better understand BPA's potential risk associations and pathological mechanisms in several chronic diabetic complications.

Multiple myeloma (MM) is a clonal plasma cell tumor originating from a post-mitotic lymphoid B-cell lineage. Bortezomib(BTZ), a first-generation protease inhibitor, has increased overall survival, progression-free survival, and remission rates in patients with MM since its clinical approval in 2003. However, the use of BTZ is challenged by the malignant features of MM and drug resistance. Polyphenols, classified into flavonoid and non-flavonoid polyphenols, have potential health-promoting activities, including anti-cancer. Previous preclinical studies have demonstrated the anti-MM potential of some dietary polyphenols. Therefore, these dietary polyphenols have the potential to be alternative therapies in anti-MM treatment regimens. This systematic review examines the synergistic effects of flavonoids and non-flavonoid polyphenols on the anti-MM impacts of BTZ. Preclinical studies on flavonoids and non-flavonoid polyphenols-BTZ synergism in MM were collected from PubMed, Web of Science, and Embase published between 2008 and 2020. 19 valid preclinical studies (Published from 2008 to 2020) were included in this systematic review. These studies demonstrated that eight flavonoids (icariin, icariside II, (-)-epigallocatechin-3-gallate, scutellarein, wogonin, morin, formononetin, daidzin), one plant extract rich in flavonoids (Punica granatum juice) and four non-flavonoid polyphenols (silibinin, resveratrol, curcumin, caffeic acid) synergistically enhanced the anti-MM effect of BTZ. These synergistic effects are mediated through the regulation of cellular signaling pathways associated with proliferation, apoptosis, and drug resistance. Given the above, flavonoids and non-flavonoid polyphenols can benefit MM patients by overcoming the challenges faced in BTZ treatment. Despite the positive nature of this preclinical evidence, some additional investigations are still needed before proceeding with clinical studies. For this purpose, we conclude by providing some suggestions for future research directions.

Rheumatoid arthritis (RA) is an essential cause of secondary sarcopenia, and patients with RA face a higher risk of developing sarcopenia. In the literature, there is a lack of reviews on animal models of RA-related sarcopenia. This review examines sarcopenia-related changes and mechanisms in induced and immune-mediated arthritis animal models and highlights potential preclinical therapies. The mechanisms for developing sarcopenia in these animal models involved inflammation, protein degradation pathways, protein synthesis, muscle regeneration and differentiation, oxidative stress, energy metabolism, and amino acid metabolism. Some anti-rheumatic drugs, supplements and nutrients, antioxidants, and physical therapy and training have been shown to improve muscle atrophy, maintain muscle mass, and prevent grip strength loss in different RA-related sarcopenia animal models. Overall, this review aims to deepen the mechanistic understanding of RA-related sarcopenia and provide a basis for developing innovative therapies.