Lipids play an important role in maintaining ovarian function.

However, excessive lipid accumulation can cause severe damage to ovarian function.

In vivo study results show that BSHXF can significantly reduce lipid accumulation in the ovaries of POI rats, while reducing the expression of lipogenic proteins PPARγ and C/EBPα, and increasing the expression of lipolytic protein ATGL and lipid β-oxidation protein CPT1A.

In vitro studies have found that the free fatty acid PA can not only reduce E2 secretion in granulosa cells, but high concentrations of PA can also significantly promote the apoptosis of GCs. BSHXF can significantly improve these changes, and is consistent with the in vivo results. BSHXF reduces lipid production in GCs, promotes lipid degradation and oxidation, and alleviates lipid accumulation.

Oxidative stress mediated by lipid accumulation is involved in the occurrence and development of various diseases (hepatitis, colon cancer, and arthritis); and studies have reported that excessive lipid accumulation can cause damage to ovarian function by inducing oxidative stress (10.1016 /j.redox.2022.102569).

This study found that BSHXF can significantly reduce lipid accumulation and ROS production in the ovaries of POI rats; at the same time, BSHXF can also significantly reverse the production of ROS in GCs induced by PA, and the therapeutic effect of BSHXF was reduced after adding ROS inducers. offset.

Interestingly, studies have found that most women have increased cardiovascular risk factors (including weight gain, visceral obesity, and elevated blood lipids) after menopause, and it has been confirmed that premature menopause (primary ovarian insufficiency) The occurrence increases the patient's risk of developing atherosclerosis. In US guidelines, factors such as premature menopause are considered cardiovascular "risk-enhancing" factors, and statin therapy is recommended for women at borderline or intermediate risk (10.1093/eurheartj/ehad472).

Literature research found that rosuvastatin, resveratrol, curcumin and berberine, natural drugs with lipid-lowering biological activity that have entered clinical trials, all have a significant improvement effect on POI (10.1177/0960327119865588) .

Therefore, POI treatment drugs combined with lipid-lowering drugs may be a new strategy for the later treatment of POI. BSHXF takes into account both, and may be an advantageous drug candidate for late-stage POI treatment.

In disease, autophagy has been described as a double-edged sword. On the one hand, autophagy contributes to cellular homeostasis by eliminating and recycling misfolded proteins or defective organelles (10.1016/j.cell.2007.12.018). On the other hand, excessive activation of autophagy is associated with cell proliferation and apoptosis resulting from excessive removal of organelles. (10.1016/j.freeradbiomed.2021.04.016)

Research shows that excessive autophagy induces the death of GCs (10.7150/ijbs.30369)

Drugs that reduce excessive autophagy improve POI

BSHXF can reduce the accumulation of LC3 in POI rats and PA-induced GCs, promote the increase of P62, and alleviate excessive autophagy. However, after incubating BSHXF and autophagy inducers together, the anti-apoptotic effect of BHSXF on GCs and the E2 secretion function were reversed, while ROS inducers and autophagy inducers acted on GCs at the same time, and the anti-apoptotic effect of BSHXF on GCs And the E2 secretion function is completely canceled.

However, studies have reported that relieving the autophagy deficiency induced by cyclophosphamide is beneficial to the survival of GCs (10.1016/j.biopha.2022.113743).

Therefore, the above situation may be due to the different ways we use to build the model, resulting in the different stages of GCs.

BSHXF can improve POI by alleviating excessive autophagy induced by lipid accumulation.