Advances in cytokine-based herbal medicine against premature ovarian insufficiency: A review

Premature ovarian insufficiency (POI) refers to a dramatic decrease in the number and/or quality of oocytes in the ovaries before the age of 40 years, and is a key cause of female infertility. The prevalence of POI has been increasing annually and tends to be younger. Researches on the etiology of POI and related pathogenesis are still very limited. Herbal medicine can treat many gynecological diseases. And herbal medicine is effective in reproductive health care such as infertility. In recent years, it has been found that immune modulation by cytokines (CK) can prevent or intervene in POI, and herbal medicine can treat POI by regulating CK to improve ovarian function and fertility. This review presents an overview of the molecular mechanisms of regulation of POI related CK, and reports the therapeutic effect of herbal medicine on POI including herbal medicine formulas, single herbal medicine, herbal medicine active components and acupuncture. This review provides theoretical support for clinical prevention and treatment of POI, and provides new ideas for researches on herbal medicine treatment of POI. We performed a collection of relevant scientific articles from different scientific databases regarding the therapeutic effect of herbal medicine on POI by regulating CK, including PubMed, Web of Science, Wanfang Database, CNKI and other publication resources. The search terms used in this review include, 'premature ovarian insufficiency', 'premature ovarian failure (POF)', 'infertility', 'herbal medicine', 'acupuncture', 'cytokine', 'interleukin (IL)', 'tumor necrosis factor-α (TNF-α)', 'interferon-γ (IFN-γ)', 'transforming growth factor-β (TGF-β)', 'vascular endothelial growth factor (VEGF)', 'immune' and 'inflammation'. This review summarized and analyzed the therapeutic effect of herbal medicine according to the existing experimental and clinical researches. The results showed that herbal medicine treats POI through CK (including ILs, TNF-α, INF-γ, VEGF, TGF-β and others) and related signaling pathways, which regulates reproductive hormones disorder, reduces ovarian inflammatory damage, oxidative stress, apoptosis and follicular atresia, improves ovarian pathological damage and ovarian reserve function. This review enriches the theory of POI treatments based on herbal medicine by regulating CK. The specific mechanisms of action and clinical researches on the treatment of POI by herbal medicine should be strengthened in order to promote the application of herbal medicine in the clinic and provide new ideas and better choices for the treatment of POI.