Natural remedies are often used as standalone treatments or as complementary approaches to modern medicine for controlling type 2 diabetes. Gardenia jasminoides, a substance used in both food and medicine, has been clinically employed in traditional Chinese medicine to treat hyperglycemia. Here, we first identified crocetin as the compound responsible for the primary hypoglycemic activity of G. jasminoides and revealed that G protein-coupled receptor kinase 5 (GRK5) is the key target through which crocetin improves glucose homeostasis and insulin resistance. To identify the bioactive components in G. jasminoides, we conducted high-resolution mass spectrometry analysis and bioactivity-guided fractionation, confirming that crocetin is the primary bioactive constituent. We demonstrated the direct binding of crocetin to GRK5 via cellular thermal shift (CETSA) and surface plasmon resonance (SPR) assays. Further knockdown experiments confirmed the essential role of GRK5 in enhancing crocetin-mediated improvements in glucose metabolism. Additionally, we explored direct downstream targets of GRK5 and demonstrated for the first time that AKT2 is a novel GRK5-interacting protein. Collectively, these findings reveal that crocetin is a promising glucose-regulating phytochemical that targets GRK5 to phosphorylate AKT2, thereby improving glucose homeostasis.

Iridoids compounds are one of the main active components of Gardenia jasminoides, which were divided into two categories: iridoid glycosides and non-glucosylated iridoids according to their chemical structures. Relevant studies have shown that components such as geniposide, deacetyl asperulosidic acid methyl ester, and geniposidic acid play an important role in anti-inflammatory, hypoglycemia, and the protection of cardiomyocytes. While the pharmacological effects of most iridoid glycosides are still not clear. This paper’s systematic summary was created by searching for relevant iridoids material on websites such as Google Scholar, PubMed, SciFinder Scholar, Science Direct, and others. Up to now, a total of 94 iridoids had been identified in G. jasminoides, among which 40 iridoids had extensive biological activities and the mechanisms involved in MAPK, NF-κB, JNK signal pathways. This paper reviews the literature on types and pharmacological effects of iridoid compounds in G. jasminoides, in order to provide a reference for its development and application.

Hyperlipidemia is a kind of lipid metabolism disease, whose pathogenesis is complex and diverse, mainly related to abnormal glucose and lipid metabolism, as well as insulin resistance and other characteristics. Because of their low toxic and side effects along with clear medicinal effects, the food and medicinal homological resources are widely used in the regulation of blood lipids in recent years. The State Administration for Market Regulation website and various databases have been searched for the use of food and medicinal homological materials in functional food products, the categories and frequency in food and medicinal homological resources, the lipid-lowering active ingredients and their mechanisms. The results showed that 53 kinds of food and medicinal homological resources were used to regulate blood lipids, of which Crataegus pinnatifida Bge., Cassia obtusifolia L., Nelumbo nucifera Gaertn., Morus alba L. and Pueraria lobata (Willd.) Ohwi were used most frequently. The main active ingredients are triterpenes and their glycosides, flavonoids, alkaloids and polysaccharides, etc., they regulated blood lipid levels and cholesterol metabolism by activating AMPK and PPARγ.

3-Epi-betulinic acid 3-O-β-D-glucopyranoside (eBAG) is a pentacyclic triterpene mainly distributed in food and medicinal plants, which exhibits various pharmacological properties. However, whether these functions are attributed to eBAG or additional components in these plants remain unknown. Herein, we report that eBAG exerted an inhibitory activity against hepatocellular carcinoma and esophageal cancer cells. EBAG induced non-apoptotic cell death in hepatocellular carcinoma cells. The eBAG-induced cell death was inhibited by knock-down of autophagy related gene (ATG) 5 and ATG7, by administration of 3-methyladenine, a selective autophagy inhibitor that suppresses phosphoinositide 3-kinase (PI3K), and by chloroquine, a classic autophagy f lux inhibitor. We demonstrated that eBAG induced an autophagy-mediated cell death. Application of eBAG mimicked cellular bioenergetics depletion leading to the reduction of intracellular ATP, activation of AMP-activated protein kinase (AMPK), and inhibition of mTOR. Co-treatment with compound C, an AMPK inhibitor, abrogated cell death induced by eBAG. We further validated the anti-tumor effect of eBAG in the murine xenograft model of hepatocellular carcinoma and found that eBAG treatment promoted the induction of autophagy and reduction of tumor growth in mice. As a functional food ingredient, eBAG is a potential therapeutic agent for the treatment of hepatocellular carcinoma and esophageal cancer.