Progress on the efficacy and mechanism of action of panax ginseng monomer saponins treat toxicity.

The value of ginsenosides in reproductive function was demonstrated in several reports. Many studies have shown that bisphenol A (BPA) can cause reproductive toxicity. Wang et al. ( Wang L. et al., 2012 ) showed that ginsenosides (75 μg/ml) significantly inhibited the decrease in cell viability and increase in apoptosis inhibited by BPA through in vitro cell culture model experiments. These effects are mediated by preventing ERK1/2 phosphorylation and enhancing cellular antioxidant capacity. Testicular toxicity is one of the side effects of chemotherapeutic drugs. Ji et al. (2007) reported the therapeutic and preventive effects of protopanaxatriol saponin (PT) on the testicular organs of male mice under toxicity induction of the chemotherapeutic drug busulfan, and the damage to spermatogenic tubules in mice injected with PT was less than that of busulfan treatment alone. These results suggest that PT is effective in recovering male reproductive organs and overcomes the toxicity of busulfan. PT may be indicated for recovering male infertility caused by azoospermia and oligospermia. Endometriosis (EMS) is an estrogen-dependent gynaecological disorder, impaired NK cell cytotoxic activity is associated with clearance obstruction of ectopic endometrial tissue in the abdominal and pelvic cavity. Zhang et al. (2018) reported that PPD-pretreated ectopic endometrial stromal cells (eESCs) enhanced the cytotoxic activity of NK cells against eESCs, reduced the number of ectopic lesions and inhibited the growth of ectopic lesions in a mouse EMS model. They suggest that this effect may be through limiting estrogen-mediated autophagy regulation and enhancing NK cell cytotoxicity.

Due to the mutual influence and restriction of various saponin monomers, the unique medicinal and health-care properties of various monomeric saponins cannot be displayed, which significantly reduces the application value. In recent years, researchers at home and abroad have devoted themselves to the use of biological methods to produce ginsenoside products and have made corresponding progress and breakthroughs in biotechnology in various research fields such as tissue culture, transgenic plants, biosynthetic pathways and synthetic biology, which have laid an essential foundation for the preparation or production of ginsenoside products in large quantities. Most ginsenoside monomers on the market are relatively cheap, such as Rb1, Re, etc. The average price is about 0.289 USD/mg; individual monomeric saponins are rarer and more costly, with an average price of about 5.797 USD/mg. This review briefly summarizes the therapeutic potential of ginsenosides in drug toxicities and exogenous toxins, and explains the mechanism of action ( Figure 1 ). Ginsenosides play an essential role in treating drug toxicity, especially in treating cancer patients, and can reduce drug toxicity and improve the survival quality of cancer patients after the cure. The underlying mechanism may be related to an increase in antioxidant enzymes and anti-apoptotic, anti-inflammatory signalling and immunostimulatory factors, as well as a decrease in pro-apoptotic, pro-inflammatory, immunosuppressive and pro-oxidant indices. Further studies revealed that this mechanism involves several signalling pathways, such as the classical antioxidant pathway: P62/KEAP1/NRF2, the apoptosis-related pathway: JNK/P53/CASPASE3, and the AMPK/mTOR signalling pathway, which plays a crucial role in the development of autophagy. In addition, ginsenosides play an essential role in the treatment of metal toxicity and the accumulation of toxins that may be caused by chemicals added to household products. In conclusion, ginsenosides are potential drugs for preventing and treating exogenous toxins. The effects of ginsenosides on the treatment of exogenous toxins. Abbreviations: ROS, reactive oxygen species; Erk, extracellular signal-regulated kinases; mTOR, mammalian target of rapamycin; LC3, light chain three; ATG5, autophagy related five; IL-1b, interleukin-1b; Nrf2, nuclear factor erythroid related factor 2; ATG3, autophagy related three; JNK, c-jun N-terminal kinase; ERK, extracellular signal-regulated kinase; COX-2, cyclooxygenase two; DMT1 + IRE, divalent metal transporter 1 with iron responsive element.

Panax ginseng C. A. Meyer (PG) has been used worldwide as a traditional medicine for thousands of years; numerous studies have shown that ginsenosides are the main active ingredients of PG. Currently, more than 150 natural ginsenosides have been isolated and identified from various parts of ginseng herbs ( Christensen, 2009 ). According to the different skeletons of ginsenoside glycosides, ginsenosides can be divided into three saponins, protopanxdiol, protopanaxtriol and oleanolic acid ( Wang et al., 2006 ). There are numerous reports on the biological effects of ginsenosides, such as immune enhancement ( Bai et al., 2019 ), hepatoprotection ( Fan et al., 2019 ), neuroprotection ( Ying et al., 2019 ), anti-inflammatory ( Chen et al., 2021 ), anti-tumour ( Liu and Fan, 2019 ), and ginsenosides also reverse the drug resistance of tumour cells caused by other chemotherapy drugs ( Meng et al., 2019 ). Different ginsenoside monomers have different functions. For example, ginsenoside Rh2 can inhibit the metastasis of cancer cells to other organs ( Shi et al., 2014 ); ginsenoside Rg1 has the effect of excitation of the central nervous system and inhibition of platelet agglutination ( Sun et al., 2016 ); ginsenoside Rg3 can inhibit the synthesis of proteins and adenine nucleoside triphosphate (ATP) in cancer cells during mitotic prophase and delay the proliferation and growth of cancer cells ( Jiang et al., 2017 ). Many western drugs are effective in the therapy treatment of diseases and play an essential role in the clinical management of tumors in particular, but their limitations are also evident; for example, the commonly used oncological drug Doxorubicin (DOX) causes cardiotoxicity. The items that contacted by us in our daily life may also contain toxic ingredients, for example, Trimethyltin in plastic stabilizers can cause neurotoxicity, and the presence of toxicity in metals such as iron and aluminum can also induce disease. Therefore, it is crucial to discover drugs from natural plants to mitigate drug toxicity and treat exogenous toxicity. This paper reviewed the effects of ginsenosides on the treatment of exogenous toxins, and we hope that this review will lay the foundation for an in-depth study of biochemical mechanisms and pharmacological impact of ginsenosides and provide a reference for further development and utilization of ginsenosides in the treatment of exogenous toxicity.