2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione, isolated from the root of Averrhoa carambola L., protects against diabetic kidney disease by inhibiting TLR4/TGFβ signaling pathway

Zhang, Hongliang; Lu, Sisi; Chen, Lixiu; Huang, Xiang; Jiang, Liping; Li, Yunchun; Liao, Peiyu; Wu, Xingchun; Zhou, Xin; Qin, Luhui; Wei, Jinbin; Huang, Renbin

doi:10.1016/j.intimp.2019.106120

Cited by 12 publications

(6 citation statements)

References 35 publications

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“…In another study from 2020, the administration of benzoquinone isolated from the roots of Averrhoa carambola to male Kunming mice with induced diabetes found a reduction in the blood glucose levels when compared with a control group (Qin et al., 2020). Zhang et al showed that the beneficial effects of Averrhoa carambola extracts in mice with induced diabetes were probably due to inhibition of the TLR4/TGF‐β signaling pathway by active compounds like DMDD (Zhang et al., 2020). So far, the evidence lies in experimental animal studies and one in vitro study (Table 1), and thus, clinical studies are needed to assess the clinical relevant antidiabetic effects in humans.…”

Section: Results and Discussion Of Trendsmentioning

confidence: 99%

Nutritional and medicinal properties of Star fruit (Averrhoa carambola): A review

Lakmal

Yasawardene

Jayarajah

et al. 2021

Food Science & Nutrition

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Star fruit (Averrhoa carambola), a popular fruit in many parts of the world, is considered to have many beneficial nutritional and medicinal effects. However, harmful nephrotoxic and neurotoxic effects have also been described. In this review, we have discussed the reported beneficial effects of star fruit, explored the potential mechanisms for such beneficial effects, and outline factors that may affect the safe level of consumption. The beneficial effects include the following: antioxidant (mediated via L‐ascorbic acid, epicatechin, and gallic acid), hypoglycemic (mediated via high fiber levels and 2‐dodecyl‐6‐methoxycyclohexa‐2,5‐diene‐1,4‐dione), hypotensive (mediated via apigenin), hypocholesterolemic (mediated via micronized fiber), anti‐inflammatory, anti‐infective, antitumor effects, and immune‐boosting effects. The presence of chronic kidney disease, gastroenteropathies, chronic pancreatitis, dehydration, consumption on an empty stomach, and higher concentration of oxalate in fruit/juice consumed predisposes to toxicity. The level of ingestion at which the beneficial effects transition to nephrotoxicity and neurotoxicity is still to be accurately ascertained. Furthermore, the relationship between the amount of star fruit ingested and the severity of toxicity is not certain and warrants further study.

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Section: Results and Discussion Of Trendsmentioning

confidence: 99%

Nutritional and medicinal properties of Star fruit (Averrhoa carambola): A review

Lakmal

Yasawardene

Jayarajah

et al. 2021

Food Science & Nutrition

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“…37 Furthermore, DMDD was also reported to be effective in reducing blood glucose levels in diabetic mice. [38][39][40] In addition, administration of benzoquinone from the roots of A. carambola L. can also reduce blood glucose levels in diabetic mice. 9 Averrhoa carambola L. fruit powder can reduce the plasma glucose level and the activity of G-6-pase in rats.…”

Section: Discussionmentioning

confidence: 99%

Averrhoa carambola L. fruit polyphenols ameliorate hyperlipidemia, hepatic steatosis, and hyperglycemia by modulating lipid and glucose metabolism in mice with obesity

et al. 2023

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BACKGROUNDHyperlipidemia, hepatic steatosis, and hyperglycemia are common metabolic complications of obesity. The objective of the present study is to investigate the in vivo protective effect of Averrhoa carambola L. fruit polyphenols (ACFP) on hyperlipidemia, hepatic steatosis, and hyperglycemia in mice with high‐fat diet (HFD)‐induced obesity and elucidate the mechanisms of action underlying the beneficial effects of ACFP. Thirty‐six specific pathogen‐free male C57BL/6J mice (4 weeks old, weighing 17.1–19.9 g) were randomly divided into three groups and fed with a low‐fat diet (LFD, 10% fat energy), HFD (45% fat energy), or HFD supplemented with ACFP by intragastric administration for 14 weeks. Obesity‐related biochemical indexes and hepatic gene expression levels were determined. The statistical analyses were conducted using one‐way analysis of variance (ANOVA) followed by Duncan's multiple range test.RESULTSThe results showed that the body weight gain, serum triglycerides, total cholesterol, glucose, insulin resistance index, and steatosis grade in the ACFP group decreased by 29.57%, 26.25%, 27.4%, 19.6%, 40.32%, and 40%, respectively, compared to the HFD group. Gene expression analysis indicated that ACFP treatment improved the gene expression profiles involved in lipid and glucose metabolism compared to the HFD group.CONCLUSIONACFP protected from HFD‐induced obesity and obesity‐associated hyperlipidemia, hepatic steatosis, and hyperglycemia by improving lipid and glucose metabolism in mice. © 2023 Society of Chemical Industry.

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“…Furthermore, according to IHC results, there were strong in situ expressions of TLR4, TGF-β1, Smad2, and Smad3 in kidney tissues, which were distinctly weakened after DMDD-treatment. Nevertheless, TGF-β1, Smad2, and Smad3 levels did not increase in the TLR4 −/− mice with significance when compared with healthy mice ( Zhang et al, 2020 ). These findings strongly suggest that TLR4 is critical for DMDD’s protective activity against renal insufficiency in diabetic mice, and hypoglycemic and anti-fibrosis properties could be regulated by the TLR4/TGF signaling pathway.…”

Section: Pharmacological Activitiesmentioning

confidence: 97%

“…Briefly, compounds 117 and 118 are identified as benzoic acid, compounds 121–125 are quinones, compounds 126 and 127 are tetrahydroisoquinoline alkaloids, and components 128–132 are identified as alkyl glycosides. Among them, 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (122) was obtained and characterized from A. carambola roots showing multiple bioactive properties both in cell and animal experimental studies, including anti-cancer ( Gao et al, 2015 ; Chen et al, 2017b ), anti-diabetic nephropathy ( Lu et al, 2019 ), anti-obesity ( Li et al, 2016 ), anti-hyperglycemic ( Zhang et al, 2020 ), anti-inflammatory ( Xie et al, 2016 ), and neuroprotective activities ( Wei et al, 2018 ).…”

Section: Nutritional and Phytochemical Compositionmentioning

confidence: 99%

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Traditional Uses, Phytochemical Constituents and Pharmacological Properties of Averrhoa carambola L.: A Review

et al. 2021

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Averrhoa carambola L. (star fruit) is an edible fruit that is extensively cultivated in southern China, Southeast Asia, India, and northern South America. It has a sweet and juicy taste and is frequently used in fruit salads and fruit platters, as a garnish in cocktail drinks and beverages, or squeezed into juice and served as a beverage. Traditionally, it has been used for treating diabetes and diabetic nephropathy, arthralgia, vomiting, lithangiuria, coughing, hangovers, and chronic paroxysmal headache for thousands of years. Currently, approximately 132 compounds have been isolated from A. carambola. Among them, flavonoids, benzoquinone, and their glycosides have been considered as biologically active substances, which are responsible for various biological activities. Pharmacological studies have revealed that crude extracts or monomeric compounds from A. carambola exhibit multiple bioactivities, such as anti-oxidant, anti-hyperglycemic, anti-obesity, anti-hyperlipidemic, anti-tumor, anti-inflammatory, hepatoprotective, cardioprotective, anti-hypertensive, neuroprotective, and others. Thus, A. carambola is a valuable treatment in Chinese medicine with therapeutic potential for multiple diseases, especially diabetes and diabetes-related diseases. Even though it is a very promising candidate in the development of functional food and the pharmaceutical industry, reports on its bioactivities have only been conducted in vivo and in vitro and there is a gap in research regarding clinical settings and safety. This review therefore provides a comprehensive and systematic overview of current progress on botany, ethnopharmacology, phytochemistry, pharmacology, and toxicity of A. carambola, providing a valuable reference for further developments and applications of A. carambola in the pharmaceutical industry and functional food.

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2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione, isolated from the root of Averrhoa carambola L., protects against diabetic kidney disease by inhibiting TLR4/TGFβ signaling pathway

Cited by 12 publications

References 35 publications

Nutritional and medicinal properties of Star fruit (Averrhoa carambola): A review

Nutritional and medicinal properties of Star fruit (Averrhoa carambola): A review

Averrhoa carambola L. fruit polyphenols ameliorate hyperlipidemia, hepatic steatosis, and hyperglycemia by modulating lipid and glucose metabolism in mice with obesity

Traditional Uses, Phytochemical Constituents and Pharmacological Properties of Averrhoa carambola L.: A Review

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