This study evaluated the effects of an aqueous extract of Caulerpa racemosa (AEC) on cardiometabolic syndrome markers, and the modulation of the gut microbiome in mice administered a cholesterol- and fat-enriched diet (CFED). Four groups of mice received different treatments: normal diet, CFED, and CFED added with AEC extract at 65 and 130 mg/kg body weight (BW). The effective concentration (EC50) values of AEC for 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and lipase inhibition were lower than those of the controls in vitro. In the mice model, the administration of high-dose AEC showed improved lipid and blood glucose profiles and a reduction in endothelial dysfunction markers (PRMT-1 and ADMA). Furthermore, a correlation between specific gut microbiomes and biomarkers associated with cardiometabolic diseases was also observed. In vitro studies highlighted the antioxidant properties of AEC, while in vivo data demonstrated that AEC plays a role in the management of cardiometabolic syndrome via regulation of oxidative stress, inflammation, endothelial function (PRMT-1/DDAH/ADMA pathway), and gut microbiota.

Green alga Caulerpa racemosa is an underexploited species of macroalgae, even though it is characterized by a green color that indicates an abundance of bioactive pigments, such as chlorophyll and possibly xanthophyll. Unlike chlorophyll, which has been well explored, the composition of the carotenoids of C. racemosa and its biological activities have not been reported. Therefore, this study aims to look at the carotenoid profile and composition of C. racemose and determine their biological activities, which include antidiabetic, anti-obesity, anti-oxidative, anti-inflammatory, and cytotoxicity in vitro. The detected carotenoids were all xanthophylls, which included fucoxanthin, lutein, astaxanthin, canthaxanthin, zeaxanthin, β-carotene, and β-cryptoxanthin based on orbitrap-mass spectrometry (MS) and a rapid ultra-high performance liquid chromatography (UHPLC) diode array detector. Of the seven carotenoids observed, it should be highlighted that β-carotene and canthaxanthin were the two most dominant carotenoids present in C. racemosa. Interestingly, the carotenoid extract of C. racemosa has good biological activity in inhibiting α-glucosidase, α-amylase, DPPH and ABTS, and the TNF-α and mTOR, as well as upregulating the AMPK, which makes it a drug candidate or functional antidiabetic food, a very promising anti-obesity and anti-inflammatory. More interestingly, the cytotoxicity value of the carotenoid extract of C. racemosa shows a level of safety in normal cells, which makes it a potential for the further development of nutraceuticals and pharmaceuticals.

Polyunsaturated fatty acids (PUFAs) are natural substances that are considered for skin protection caused by UVB exposure. The increased levels of photoaging and inflammation markers, i.e. matrix metalloproteinases (MMPs), cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) are correlated with the signs of photoaging and inflammation in the skin. Tempeh, one of the Indonesian fermented foods is a promising source of PUFAs for food applications including nutraceuticals and cosmeceuticals. In this study, PUFA-rich oil was extracted from white and black soybean tempeh and tested on its efficacy on down-regulating several genes related to photoaging and inflammation in UVB-irradiated premature skin aging in mice model by conducting hematoxylin and eosin (H&E) staining and quantitative Real Time-PCR (qRT-PCR) assays. Tempeh oil was extracted in methanol and chloroform using Bligh and Dyer method, and PUFA constituents in tempeh oil were determined by pyrolysis gas chromatography-mass spectrometry (py/GC-MS) analysis. Mice skin dorsal was irradiated with UVB gradually for 4 weeks to induce premature photoaging. Mice were grouped into negative control; positive control; black soybean tempeh oil at 100 and 300 mg/kg; white soybean tempeh oil at 100 and 300 mg/kg; and omega 3 standard. Mice were orally supplemented with tempeh oil for 4 weeks along with UVB irradiation. The py/GC-MS profiling revealed that both tempeh oils contained major linoleic acid PUFA with 52.3% in white tempeh oil and 85.69% in black tempeh oil, respectively. H&E staining demonstrated that UVB irradiation caused premature skin photoaging in mice, indicating by necrosis, epidermal atrophy, and tissue damage. Orally tempeh oil treatment improved tissue damage and increased the proliferation of hair follicle in the skin. Tempeh oil was found to be effectively inhibited the genes expression of MMP-1, MMP-3, MMP-9, COX-2 and iNOS in UVB-irradiated mice skin. Among these genes, tempeh oil from black and white soybean tempeh exerted a significant effect on down-regulating the expression of MMP-9 gene in UVB-irradiated mice skin. In conclusion, tempeh oil may offer the promising photoprotective ingredient in application of nutraceuticals and cosmeceuticals for protecting skin photoaging.

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Post-transplantation nonalcoholic fatty liver disease (NAFLD) is common in liver transplant recipients. Changes in the expression levels and activities of drug-metabolizing enzymes and drug transporters have been reported in patients with NAFLD and relevant rodent models. Here, we evaluated whether the pharmacokinetics of mycophenolic acid (MPA), an immunosuppressant, would be altered in rats with NAFLD. NAFLD was induced by feeding a diet containing 1% (w/w) orotic acid for 20 days. The extent of hepatic glucuronidation of MPA to a major metabolite, mycophenolic acid-7-O-glucuronide (MPAG), did not differ between rats with NAFLD and controls. The expression levels of hepatic multidrug resistance-associated protein 2, responsible for biliary excretion of MPAG, were comparable in rats with NAFLD and controls; the biliary excretion of MPAG was also similar in the two groups. Compared with control rats, rats with NAFLD did not exhibit significant changes in the areas under the plasma concentration – time curves of MPA or MPAG after intravenous (5 mg/kg) or oral (10 mg/kg) administration of MPA. However, delayed oral absorption of MPA was observed in rats with NAFLD compared with controls; the MPA and MPAG peak plasma concentrations fell significantly and the times to achieve them were prolonged following oral administration of MPA.