Supplementation of Abelmoschus manihot Ameliorates Diabetic Nephropathy and Hepatic Steatosis by Activating Autophagy in Mice

Abstract

Diabetic nephropathy (DN) is a diabetic complication marked by albuminuria and a decline of the glomerular filtration rate. Diabetic kidneys are defective in the autophagy process and mitochondrial function and their enhancement of activity alleviates the pathology. In this paper, we developed a mouse model of DN by a combined treatment of a high-fat diet and streptozotocin after unilateral nephrectomy and supplementation with flower or leaf extracts of Abelmoschus manihot (AM) were tested. The preventive effects of the extracts on DN pathology and changes on autophagy and mitochondrial proteins were investigated. DN mice showed a significant increase in fasting blood glucose, plasma creatinine, blood urea nitrogen, and urinary albumin levels. Periodic acid–Schiff and Sirius red staining of the diabetic kidney presented a significant change in glomerular and tubular structures that was associated with podocyte loss and fibrotic protein accumulation. These changes were attenuated by AM extract treatment in DN mice. In addition, hepatic injury, proinflammatory cytokines, and lipid accumulation were decreased by AM extracts in DN mice. As a protective mechanism, AM extracts significantly increased the expression of proteins by regulating autophagy and mitochondrial dynamics, which potentially prevented the kidney and liver from accumulating pathogenic proteins and dysfunctional mitochondria, which alleviated the progression of DN.

Traditional Uses, Chemical Constituents, Biological Properties, Clinical Settings, and Toxicities of Abelmoschus manihot L.: A Comprehensive Review

“…for 35 days) markedly reduced the levels of plasma creatinine, BUN, and urinary albumin. Moreover, the kidney/body weight ratio also increased in mice with DN in comparison with control mice ( Kim et al., 2018 ).…”

“…A. manihot is mainly distributed in tropical areas, especially Asia and the Pacific Islands. Its flowers and leaves are edible and have medicinal effects, and they have been traditionally used to treat inflammation, pain, urinary infections, and chronic bronchitis because of their anti-inflammatory, antiviral, antibacterial, and wound-healing properties ( Yang et al., 2015 ; Rubiang-Yalambing et al., 2016 ; Kim et al., 2018 ). In eastern Indonesia, the South Pacific Islands, and Papua New Guinea, A. manihot is regarded as an edible hibiscus and is consumed as a popular leafy vegetable because it contains high levels of nutrients such as Ca, Fe, K, Mg, Mn, Na, Zn, Cu, folate, and β-carotene ( Rubiang-Yalambing et al., 2016 ).…”

“…In Korea, A. manihot has been used to make the traditional form of paper known as hanji. It was previously recognized as a species of hibiscus, although it is now classified in the genus Abelmoschus and its scientific name is Abelmoschus manihot ( Kim et al., 2018 ).…”

“…for 84 days) notably decreased the levels of serum creatinine and BUN by downregulating the expression of IL-1, IL-2, IL-6, and TNF-α in a dose-dependent manner by suppressing the activation of the iRhom2/TNF-α-converting enzyme signaling pathway in a rat model of DN induced by unilateral nephrectomy and STZ injections in comparison with 4-phenylbutanoic acid (2.5 mg/kg) as a positive control ( Liu et al., 2018 ). Kim et al. (2018) established a mouse model of DN induced by a high-fat diet and STZ after unilateral nephrectomy.…”

Extraction and determination of bioactive flavonoids from Abelmoschus manihot (Linn.) Medicus flowers using deep eutectic solvents coupled with high‐performance liquid chromatography

“…flowers, leaves, and stems) of A. manihot have good medicinal value . Especially, A. manihot flowers, which are commonly consumed as a healthy beverage in China, have been demonstrated to have many pharmacological effects such as treatment of diabetic nephropathy and chronic kidney disease . Moreover, the flower extract also has effect on regulation of lipid metabolism , treatment of oral ulcers , etc.…”