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. 2022 Apr 4;13:876183. doi: 10.3389/fphar.2022.876183

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Copyright © 2022 Hossain, Yousaf, Liu, Chang and Zhou.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Combined therapy of Malaysian propolis and metformin achieved the most prominent results in treating diabetes, diabetic nephropathy, attenuating hepatic, testicle injury, and subfertility/infertility in diabetic mice in comparison to the mono-therapeutic interventions. The possible mechanistic actions in attenuating hyperglycemia and diabetes-related renal, hepatic, and testicle damage were related to 1) increased insulin sensitivity and glucose uptake; 2) reduced inflammation via NF-κB pathway; 3) antioxidant and reduced oxidative damage via activating Nrf2-regulated antioxidant genes. The therapeutic benefits for subfertility and infertility were related to regulated serum, intratesticular free testosterone, testicular lactate metabolism, and spermatogenesis and mating behavior. Black arrows represent the action of metformin in the combination, whereas brown arrows represent the action of propolis.