Total flavonoids extracted from Nervilia Fordii function in polycystic ovary syndrome through IL-6 mediated JAK2/STAT3 signaling pathway

Biosci Rep. 2019 Jan 3;39(1):BSR20181380. doi: 10.1042/BSR20181380. Print 2019 Jan 31.

Abstract

Large doses of flavonoids could cure many diseases with no serious side effects. However, the role of flavonoids in the treatment of polycystic ovary syndrome (PCOS) has not been reported. Therefore, total flavonoids extracted from Nervilia Fordii were selected to explore its therapeutic efficiency in PCOS. PCOS rat model was constructed to explore the role of total flavonoids in the treatment of PCOS. ELISA was used to assess the changes of ovulation function under the treatment of total flavonoids with or without exogenous interleukin-6 (IL-6). Western blot, real-time PCR and immunohistochemistry were carried out to assess the related molecular mechanisms. We explored that total flavonoids obviously increased the serum levels of follicle-stimulating hormone (FSH), and sharply decreased the serum levels of luteinizing hormone (LH), testosterone (T) and insulin (INS) in the PCOS-IR rats via partly inhibiting the activation of JAK2/STAT3 pathway, partially up-regulating the IL-6 expression and partially down-regulating the suppressor of cytokine signaling 3 (SOCS3) expression in ovaries of PCOS rats. The effect of total flavonoids on estrous cycles, serum levels of FSH, LH, T and INS were partially attenuated by IL-6 in PCOS rat model. Moreover, IL-6 significantly reversed the effect of total flavonoids on the phosphorylation of JAK2/STAT3, the expression of IL-6 and SOCS3 in ovaries of PCOS rats. Total flavonoids extracted from Nervilia Fordii might induce the expression of IL-6 in ovary and act as a potential therapeutic drug for the treatment of PCOS.

Keywords: flavonoids; interleukin-6; ovary; polycystic ovary syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Blood Glucose
  • Chorionic Gonadotropin / administration & dosage
  • Disease Models, Animal
  • Estrous Cycle / drug effects
  • Female
  • Flavonoids / isolation & purification
  • Flavonoids / pharmacology*
  • Follicle Stimulating Hormone / blood
  • Follicle Stimulating Hormone / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Insulin / administration & dosage
  • Insulin / blood
  • Insulin Resistance
  • Interleukin-6 / blood
  • Interleukin-6 / genetics*
  • Interleukin-6 / pharmacology
  • Janus Kinase 2 / blood
  • Janus Kinase 2 / genetics*
  • Luteinizing Hormone / blood
  • Luteinizing Hormone / genetics
  • Orchidaceae / chemistry*
  • Ovulation / drug effects
  • Plant Extracts / chemistry
  • Polycystic Ovary Syndrome / chemically induced
  • Polycystic Ovary Syndrome / drug therapy*
  • Polycystic Ovary Syndrome / genetics
  • Polycystic Ovary Syndrome / pathology
  • Rats
  • Rats, Sprague-Dawley
  • STAT3 Transcription Factor / blood
  • STAT3 Transcription Factor / genetics*
  • Signal Transduction
  • Testosterone / blood
  • Testosterone / genetics

Substances

  • Antineoplastic Agents, Phytogenic
  • Blood Glucose
  • Chorionic Gonadotropin
  • Flavonoids
  • Il6 protein, rat
  • Insulin
  • Interleukin-6
  • Plant Extracts
  • STAT3 Transcription Factor
  • Stat3 protein, rat
  • Testosterone
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • Jak2 protein, rat
  • Janus Kinase 2