Ginsenosides are major bioactive compounds present in the Panax species. Ginsenosides exhibit various pharmaceutical properties, including anticancer, anti-inflammatory, antimetastatic, hypertension, and neurodegenerative disorder activities. Although several commercial products have been presented on the market, most of the current chemical processes have an unfriendly environment and a high cost of downstream processing. Compared to plant extraction, microbial production exhibits high efficiency, high selectivity, and saves time for the manufacturing of industrial products. To reach the full potential of the pharmaceutical resource of ginsenoside, a suitable microorganism has been developed as a novel approach. In this review, cell biological mechanisms in anticancer activities and the present state of research on the production of ginsenosides are summarized. Microbial hosts, including native endophytes and engineered microbes, have been used as novel and promising approaches. Furthermore, the present challenges and perspectives of using microbial hosts to produce ginsenosides have been discussed.

Compound K (CK) is one of the major metabolites found in mammalian blood and organs following oral administration of Panax plants. CK, also known as minor ginsenoside, can be absorbed in the systemic circulation. It has garnered significant attention in healthcare and medical products due to its pharmacological activities, such as antioxidation, anticancer, antiproliferation, antidiabetics, neuroprotection, and anti-atherogenic activities. However, CK is not found in natural ginseng plants but in traditional chemical synthesis, which uses toxic solvents and leads to environmental pollution during the harvest process. Moreover, enzymatic reactions are impractical for industrial CK production due to low yield and high costs. Although CK could be generated from major ginsenosides, most ginsenosides, including protopanaxatriol-oleanane and ocotillol-type, are not converted into CK by catalyzing β-glucosidase. Therefore, microbial cell systems have been used as a promising solution, providing a safe and efficient approach to CK production. This review provides a summary of various approaches for the production of CK, including chemical and enzymatic reactions, biotransformation by the human intestinal bacteria and endophytes as well as engineered microbes. Moreover, the approaches for CK production have been discussed to improve the productivity of target compounds.

Echinochrome A (EchA) is a natural bioproduct extracted from sea urchins, and is an active component of the clinical drug, Histochrome®. EchA has antioxidant, anti-inflammatory, and antimicrobial effects. However, its effects on diabetic nephropathy (DN) remain poorly understood. In the present study, seven-week-old diabetic and obese db/db mice were injected with Histochrome (0.3 mL/kg/day; EchA equivalent of 3 mg/kg/day) intraperitoneally for 12 weeks, while db/db control mice and wild-type (WT) mice received an equal amount of sterile 0.9% saline. EchA improved glucose tolerance and reduced blood urea nitrogen (BUN) and serum creatinine levels but did not affect body weight. In addition, EchA decreased renal malondialdehyde (MDA) and lipid hydroperoxide levels, and increased ATP production. Histologically, EchA treatment ameliorated renal fibrosis. Mechanistically, EchA suppressed oxidative stress and fibrosis by inhibiting protein kinase C-iota (PKCι)/p38 mitogen-activated protein kinase (MAPK), downregulating p53 and c-Jun phosphorylation, attenuating NADPH oxidase 4 (NOX4), and transforming growth factor-beta 1 (TGFβ1) signaling. Moreover, EchA enhanced AMPK phosphorylation and nuclear factor erythroid-2-related factor 2 (NRF2)/heme oxygenase 1 (HO-1) signaling, improving mitochondrial function and antioxidant activity. Collectively, these findings demonstrate that EchA prevents DN by inhibiting PKCι/p38 MAPK and upregulating the AMPKα/NRF2/HO-1 signaling pathways in db/db mice, and may provide a therapeutic option for DN.