Updated Pharmacological Effects, Molecular Mechanisms, and Therapeutic Potential of Natural Product Geniposide

Abstract

At present, the potential of natural products in new drug development has attracted more and more scientists’ attention, and natural products have become an important source for the treatment of various diseases or important lead compounds. Geniposide, as a novel iridoid glycoside compound, is an active natural product isolated from the herb Gardenia jasminoides Ellis (GJ) for the first time; it is also the main active component of GJ. Recent studies have found that geniposide has multiple pharmacological effects and biological activities, including hepatoprotective activity, an anti-osteoporosis effect, an antitumor effect, an anti-diabetic effect, ananti-myocardial dysfunction effect, a neuroprotective effect, and other protective effects. In this study, the latest research progress of the natural product geniposide is systematically described, and the pharmacological effects, pharmacokinetics, and toxicity of geniposide are also summarized and discussed comprehensively. We also emphasize the major pathways modulated by geniposide, offering new insights into the pharmacological effects of geniposide as a promising drug candidate for multiple disorders.

Glutathione S-Transferases Mediate In Vitro and In Vivo Inactivation of Genipin: Implications for an Underlying Detoxification Mechanism

“…Although the exact mechanisms of GE-induced liver injury need to be clarified, it is generally accepted that the reactive metabolite of GE, genipin (GP), is the main constituent causing hepatotoxicity. 9,10 Normally, the formation of reactive metabolites in herbal medicines or dietary supplements is mediated by hepatic cytochrome P450 or intestinal bacteria. The reactive species formed can covalently bind to cellular macromolecules, including proteins, DNA, and lipids, subsequently triggering toxicity in various manners.…”

“…However, GE has been reported to cause hepatotoxicity in both in vivo and in vitro studies. , According to published data, three consecutive days of 280 mg/kg or a single dose of 574 mg/kg GE resulted in hepatotoxicity in rats. Although the exact mechanisms of GE-induced liver injury need to be clarified, it is generally accepted that the reactive metabolite of GE, genipin (GP), is the main constituent causing hepatotoxicity. , …”

Effects of Ferroptosis on Cardiovascular Diseases

“…Last but not least, geniposide, an active compound mostly obtained from Gardenia jasminoides Ellis, exhibits anti-inflammatory, antioxidant, antithrombotic, and ameliorative effects on the disturbance of glucose and lipid metabolism. It has been used to treat a variety of chronic inflammatory disorders, and by activating GPX4, it can reduce myocardial infarction by regulating the oxidative stress and ferroptosis driven on by iron overload [ 109 – 112 ].…”

Iridoid‐glycoside isolation and purification from Premna fulva leaves

“…Four iridoid glycosides and four lignans, including three new iridoid glycosides ( 4 – 6 ) and five known compounds ( 1 – 3 , 7 , and 8 ) (Figure 1, Figure S4), were effectively separated and purified. In vitro analysis using lipopolysaccharide (LPS)‐induced RAW 264.7 cells confirmed the anti‐inflammatory activity of the extracted iridoid glycosides [21].…”