Abstract
Ligustri Lucidi Fructus (LLF), the dry and ripe fruit of Ligustrum lucidum W. T. Aiton (Oleaceae), is a traditional Chinese medicine for nourishing the liver and kidney in clinics for thousands of years. Wine-steamed Ligustri Lucidi Fructus (WLL) can alleviate coolness and smoothness of LLF and enhance the function of nourishing the liver and kidney, so ancient and modern medicine usually used it in clinics. First of all, we prepared the extracts of different polar fractions of WLL to explore the effective fractions and potential mechanisms of WLL in the treatment of diabetic nephropathy (DN). Then, HPLC method was used to determine the contents of 12 active components in WLL and its different polar components. Finally, the potential relationship between 12 active components and physicochemical parameters of DN rats was explored. The pharmacological experiments showed that WLL, ethyl acetate (EtOAc), and n-butanol (n-BuOH) extracts not only significantly alleviated the clinical symptoms and kidney damage of DN rats but also had obvious anti-inflammatory and antioxidant effects. In addition, the results of HPLC analysis showed that the 12 active components of WLL mainly existed in the extracts of EtOAc and n-BuOH. The Pearson correlation analysis showed 12 active components and physicochemical parameters had different degrees of correlation. In conclusion, we proved that the extracts of EtOAc and n-BuOH were the effective fractions of WLL in treating DN in rats, and they could regulate the levels of inflammatory cytokines and decrease oxidation stress, which provides a basis for further research on the mechanism of WLL in treating DN and provides a pharmacological and chemical foundation for the development of new anti-DN drugs.
Highlights
Diabetic nephropathy (DN) is one of the systemic microvascular complications of diabetes, which is accompanied by proteinuria [1]. e main pathological changes caused by DN include glomerular hypertrophy, extracellular matrix accumulation, and basement membrane thickening, which lead to glomerular sclerosis or renal interstitial fibrosis, accompanied by proteinuria, renal insufficiency, and dyslipidemia. e pathogenesis of DN is complex, including glucose and lipid metabolism disorders, renal hemodynamics abnormalities, inflammatory response with abnormal cytokine activity, oxidative stress, and other factors [2]
The kidney histoarchitecture under the light microscopic observations showed no abnormal features (Figure 7(a)). e model group showed significant kidney damage, such as glomerular atrophy and localized fibrosis, inflammatory cell infiltration, partial degeneration of the renal tubular epithelium, and interstitial hyperemia (Figure 7(b)), indicating that the DN model was successful. e kidney morphological architecture abnormalities were restored by administering Wine-steamed Ligustri Lucidi Fructus (WLL), EtOAc, and n-BuOH extracts and Mef for 12 weeks (Figures 7(c), 7(e), 7(f ), and 7(h)) compared with model group, indicating that WLL, EtOAc, n-BuOH, and Mef groups had significant kidney protective effects. e PE group and water group showed obvious glomerular congestion, renal tubular granule degeneration, and glomerular adhesion, which showed no significant improvement compared with the model group (Figures 7(d) and 7(g))
We found that WLL, EtOAc, and n-BuOH extracts and Mef could reduce the levels of TG, total serum cholesterol (TC), and low-density lipoprotein cholesterin (LDL-C) and increase the level of high-density lipoprotein cholesterol (HDL-C), indicating that they had the ability to regulate lipid metabolism
Summary
Diabetic nephropathy (DN) is one of the systemic microvascular complications of diabetes, which is accompanied by proteinuria [1]. e main pathological changes caused by DN include glomerular hypertrophy, extracellular matrix accumulation, and basement membrane thickening, which lead to glomerular sclerosis or renal interstitial fibrosis, accompanied by proteinuria, renal insufficiency, and dyslipidemia. e pathogenesis of DN is complex, including glucose and lipid metabolism disorders, renal hemodynamics abnormalities, inflammatory response with abnormal cytokine activity, oxidative stress, and other factors [2].Ligustri Lucidi Fructus (LLF; Figure S1B) is the dried fruit of Ligustrum lucidum W. T. Aiton (Figure S1A) in the Oleaceae family [3]. Aiton (Figure S1A) in the Oleaceae family [3] It is mainly found in Hunan, Sichuan, Jiangsu, and Zhejiang provinces in China [4] and is mostly used to nourish the liver and kidney. E main LLF active components include phenylethanoids, iridoid glycosides, triterpenoids, and others [8]. Phenylethanoid components include salidroside, tyrosinol, hydroxyltyrosinol, acteoside, and echinacoside [9], which have anti-inflammatory activities, anticancer activities, Evidence-Based Complementary and Alternative Medicine lowering blood sugar and blood lipid, and so on [10,11,12]. E iridoid glycosides components, including specnuezhenide, ligustroside G13 (G13), oleonuezhenide, nuezhenidic acid, neonuezhenide, 1′′-O-β-D-glucosylformoside, and oleuropein, were reported for lowering blood lipids [13]. Triterpenoids mainly consist of oleanolic acid and ursolic acid, which have antitumor, hepatoprotective, and antiosteoporosis effects [14, 15]
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