Cucurbitane Triterpenoids from the Fruits of <i>Momordica Charantia</i> Improve Insulin Sensitivity and Glucose Homeostasis in Streptozotocin‐Induced Diabetic Mice

Han, Joo‐Hui; Tuấn, Nguyễn Quốc; Park, Min‐Ho; Quan, Khong Trong; Oh, Joonseok; Heo, Kyung‐Sun; Na, MinKyun; Myung, Chang‐Seon

doi:10.1002/mnfr.201700769

Cited by 47 publications

(28 citation statements)

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“…Evidence from mechanistic studies in diabetic rodents indicates that bitter melon enhances insulin sensitivity by decreasing serum levels of the pro-inflammatory modulators tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), decreasing expression of suppressor of cytokine signaling-3 (SOCS-3) and c-Jun N-terminal kinase (JNK), and augmenting insulin-stimulated tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1) [ 27 , 30 ]. Multiple studies in male rodents from our laboratories and others demonstrate that bioactives in bitter melon improve insulin sensitivity, possibly via reduced skeletal muscle and hepatic lipid accumulation [ 31 – 33 ]. The effect of bitter melon extract on hepatic lipids is attributed to reduced glucose production and lipid synthesis in the liver [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

Potential adverse effects of botanical supplementation in high-fat-fed female mice

Fuller

Mendoza

et al. 2018

Biol Sex Differ

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BackgroundInsulin resistance underlies metabolic syndrome and is associated with excess adiposity and visceral fat accumulation, which is more frequently observed in males than females. However, in young females, the prevalence of metabolic syndrome is rising, mainly driven by accumulation of abdominal visceral fat. The degree to which sex-related differences could influence the development of insulin resistance remains unclear, and studies of potential therapeutic strategies to combat metabolic syndrome using rodent models have focused predominantly on males. We therefore evaluated the effects of two nutritional supplements derived from botanical sources, an extract of Artemisia dracunculus L. (termed PMI5011) and Momordica charantia (commonly known as bitter melon), on female mice challenged with a high-fat diet in order to determine if dietary intake of these supplements could ameliorate obesity-induced insulin resistance and metabolic inflexibility in skeletal muscle.MethodsBody composition, physical activity and energy expenditure, fatty acid oxidation, insulin signaling, and gene and protein expression of factors controlling lipid metabolism and ectopic lipid accumulation were evaluated in female mice fed a high-fat diet supplemented with either PMI5011 or bitter melon. Statistical significance was assessed by unpaired two-tailed t test and repeated measures ANOVA.ResultsPMI5011 supplementation resulted in increased body weight and adiposity, while bitter melon did not induce changes in these parameters. Pyruvate tolerance testing indicated that both supplements increased hepatic glucose production. Both supplements induced a significant suppression in fatty acid oxidation in skeletal muscle homogenates treated with pyruvate, indicating enhanced metabolic flexibility. PMI5011 reduced lipid accumulation in skeletal muscle, while bitter melon induced a downward trend in lipid accumulation in the skeletal muscle and liver. This was accompanied by transcriptional regulation of autophagic genes by bitter melon in the liver.ConclusionsData from the current study indicates that dietary supplementation with PMI5011 and bitter melon evokes a divergent, and generally less favorable, set of metabolic responses in female mice compared to effects previously observed in males. Our findings underscore the importance of considering sex-related variations in responses to dietary supplementation aimed at combating metabolic syndrome.Electronic supplementary materialThe online version of this article (10.1186/s13293-018-0199-1) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Potential adverse effects of botanical supplementation in high-fat-fed female mice

Fuller

Mendoza

et al. 2018

Biol Sex Differ

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“…[25][26][27] For example, new cucurbitane-type triterpenoids have shown potential for the prevention and management of diabetes by improving insulin sensitivity and glucose homeostasis. 28 Triterpenoids, such as cyclocaric acid B and cyclocarioside H, extracted from C. paliurus leaves, promote glucose uptake in the absence of insulin, and ameliorate inammation by inhibiting the insulin receptor substrate 1 (IRS-1)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway. 29 However, no C. paliurus triterpenoids with antidiabetic effects or their specic targets have been described.…”

Section: Introductionmentioning

confidence: 99%

Network pharmacology-based study of the mechanisms of action of anti-diabetic triterpenoids from Cyclocarya paliurus

Zhang

Tong

et al. 2020

RSC Adv.

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“…Further experiments extended these findings in males to demonstrate early dietary supplementation with PMI5011 protects against insulin resistance and ectopic lipid accumulation in the liver and skeletal muscle and that these effects are independent of any changes in adiposity or body mass [ 16 ]. Additional studies in male rodents showed that Momordica charantia , commonly known as bitter melon, acts as an insulin sensitizer by diminishing hepatic and skeletal muscle lipid accumulation and by reducing hepatic glucose production and lipogenesis [ 17 , 18 , 19 , 20 ]. Although these studies support the idea that botanical dietary supplements derived from sources such as Artemisia dracunculus L. and Momordica charantia can exert metabolically desirable effects in male mice exhibiting the risk factors for MetS [ 16 , 21 ], the beneficial effects may not be recapitulated in female mice exposed to a high-fat diet [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Adaptive Fat Oxidation Is Coupled with Increased Lipid Storage in Adipose Tissue of Female Mice Fed High Dietary Fat and Sucrose

Fuller

Mendoza

et al. 2020

Nutrients

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Western diets high in fat and sucrose are associated with metabolic syndrome (MetS). Although the prevalence of MetS in women is comparable to that in men, metabolic adaptations in females to Western diet have not been reported in preclinical studies. This study investigates the effects of Western diet on risk factors for MetS in female mice. Based on our earlier studies in male mice, we hypothesized that dietary supplementation with extracts of Artemisia dracunculus L. (PMI5011) and Momordica charantia (bitter melon) could affect MetS risk factors in females. Eight-week-old female mice were fed a 10% kcal fat, 17% kcal sucrose diet (LFD); high-fat, high-sucrose diet (HFS; 45% kcal fat, 30% kcal sucrose); or HFS diet with PMI5011 or bitter melon for three months. Body weight and adiposity in all HFS groups were greater than the LFD. Total cholesterol level was elevated with the HFS diets along with LDL cholesterol, but triglycerides and free fatty acids were unchanged from the LFD. Over the three month period, female mice responded to the HFS diet by adaptive increases in fat oxidation energy in muscle and liver. This was coupled with increased fat storage in white and brown adipose tissue depots. These responses were enhanced with botanical supplementation and confer protection from ectopic lipid accumulation associated with MetS in female mice fed an HFS diet.

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Cucurbitane Triterpenoids from the Fruits of Momordica Charantia Improve Insulin Sensitivity and Glucose Homeostasis in Streptozotocin‐Induced Diabetic Mice

Abstract: Our findings demonstrate that the new cucurbitane-type triterpenoids have potential for prevention and management of diabetes by improving insulin sensitivity and glucose homeostasis.

Cited by 47 publications

References 38 publications

Potential adverse effects of botanical supplementation in high-fat-fed female mice

Potential adverse effects of botanical supplementation in high-fat-fed female mice

Network pharmacology-based study of the mechanisms of action of anti-diabetic triterpenoids from Cyclocarya paliurus

Adaptive Fat Oxidation Is Coupled with Increased Lipid Storage in Adipose Tissue of Female Mice Fed High Dietary Fat and Sucrose

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