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Lipopolysaccharide (LPS), a well-conserved cell wall component of Gram positive bacteria, exerts its toxic effects via inducing oxidative and pro-inflammatory responses. Red palm oil (RPO) is a unique natural product with a balanced ratio of saturated and unsaturated fatty acids, with reported antioxidant and anti-inflammatory effects. In this study, we assess the protective effect and mechanistic action of RPO using a lipopolysaccharide (LPS)-induced hepatic injury model. Male Wistar rats were assigned into four groups (10 animals/group): normal control (NC), RPO, LPS and RPO + LPS. Animals in the RPO and RPO + LPS groups were administered RPO (200 μL/day) for 28 days. On the 27th day of experiment, animals in LPS and RPO + LPS groups were injected with LPS (0.5 mg/kg body weight). Animals were sacrificed 24 h later, and blood and liver tissues harvested for biochemical and molecular analysis. RPO resolved hepatic histological dysfunction induced by LPS, and lowered alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and γ-glutamyl transferase activities in the serum. Hepatic malondialdehyde and conjugated dienes, as well as pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6 and TNFα were significantly diminished (p < 0.05) by RPO pre-treatment. Activity of hepatic antioxidant enzymes including superoxide dismutase, glutathione reductase, glutathione peroxidase, as well as glutathione redox status (GSH:GSSG), and markers of antioxidant capacity that decreased as a result of LPS injection were improved by RPO pre-treatment. Mechanistically, RPO up-regulated mRNA expression of redox sensitive transcription factor Nrf2 and its downstream targets GCL and HO-1, while also suppressing the expression of NFκβ and associated inflammatory protein, Iκβ kinase (IκKβ). In conclusion, this study highlights the ameliorating effects of RPO against LPS-induced hepatic injury and revealed the Nrf2/GCL/HO-1 and NFκβ signaling axis as potential contributing mechanisms.

Shortage in insulin secretion or degradation of produced insulin is the principal characteristic of the metabolic disorder of diabetes mellitus (DM). However, because the current medications for the treatment of DM have many detrimental side effects, it is necessary to develop more effective antidiabetic drugs with minimal side effects. Alpha-glucosidase and alpha-amylase inhibitors are directly implicated in the delay of carbohydrate digestion. Pharmacologically, these inhibitors could be targeted for the reduction in glucose absorption rate and, subsequently, decreasing the postprandial rise in plasma glucose and the risk for long-term diabetes complications. The main objectives of this research study were to isolate different phytochemical constituents present in the methanolic extract of Plectranthusecklonii and evaluate their alpha-glucosidase and alpha-amylase inhibitory activities and antioxidant capacity. The phytochemical investigation of the methanolic extract of P. ecklonii yielded three known compounds, viz. parvifloron D, F, and G (1–3, respectively). Parvifloron G was isolated for the first time from P. ecklonii. The in vitro bio-evaluation of the methanolic extract of P. ecklonii and its isolated compounds against alpha-glucosidase showed that 3 exhibited moderate inhibitory activity with IC50 values of 41.3 ± 1.2 μg/mL. Molecular docking analysis confirmed the alpha-glucosidase inhibitory activity demonstrated by 3. Additionally, strong antioxidant capacities were demonstrated by 3 and 1 on ORAC (28726.1 ± 8.1; 3942.9.6.6 ± 0.1 µM TE/g), respectively, which were comparable with the reference antioxidant epigallocatechingallate (EGCG). Furthermore, 3 also showed strong activity on TEAC (3526.1 ± 0.6 µM TE/g), followed by 2 (1069.3 ± 2.4 µM TE/g), as well as on FRAP (1455.4 ± 2.0 µM AAE/g). The methanolic extract of P. ecklonii is a rich source of abietane diterpenes with strong antioxidant activities. This is the first scientific report on alpha-glucosidase and alpha-amylase inhibitory activities, molecular docking, and antioxidant capacities of P. ecklonii constituents.

Diabetes mellitus (DM) is one of the most dangerous metabolic diseases with a high rate of mortality worldwide. It is well known that insulin resistance and deficiency in insulin production from pancreatic β-cells are the main characteristics of DM. Due to the detrimental side effects of the current treatment, there is a considerable need to develop new effective antidiabetic drugs, especially alpha-glucosidase and alpha-amylase inhibitors with lesser adverse effects. These inhibitors are known to be directly involved in the delay of carbohydrate digestion, resulting in a reduction of glucose absorption rate and, consequently, reducing the postprandial rise of plasma glucose, which can reduce the risk of long-term diabetes complications. Furthermore, natural products are well-known sources for the discovery of new bioactive compounds that can serve as scaffolds for drug discovery, including that of new antidiabetic drugs. The phytochemical investigation of Salvia aurita collected from Hogobach Pass, Eastern Cape Province, South Africa (SA), yielded four known abietane diterpenes namely carnosol (1), rosmanol (2), 7-methoxyrosmanol (3), 12-methoxycarnosic acid (4), and one flavonoid named 4,7-dimethylapigenin (5). Structural characterization of these isolated compounds was conducted using 1 and 2D NMR, in comparison with reported spectroscopic data. These compounds are reported for the first time from S. aurita. The biological evaluation of the isolated compound against alpha-glucosidase exhibited strong inhibitory activities for 3 and 2 with the half maximal inhibitory concentration (IC50) values of 4.2 ± 0.7 and 16.4 ± 1.1 µg/mL respectively, while 4 and 1 demonstrated strong alpha-amylase inhibitory activity amongst the isolated compounds with IC50 values of 16.2 ± 0.3 and 19.8 ± 1.4 µg/mL. Molecular docking analysis confirms the strong inhibitory activity of 3 against alpha-glucosidase. Additionally, excellent antioxidant capacities were displayed by 2, 1, and 3, respectively, with oxygen radical absorbance capacity (ORAC) (25.79 ± 0.01; 23.96 ± 0.01; 23.94 ± 0.02) mM Trolox equivalent (TE)/g; 1 and 2 as ferric-ion reducing antioxidant power (FRAP) (3.92 ± 0.002; 1.52 ± 0.002) mM ascorbic acid equivalent (AAE)/g; 5 and 2 as Trolox equivalent absorbance capacity (TEAC) (3.19 ± 0.003; 2.06 ± 0.003) mM TE/g. The methanolic extract of S. aurita is a rich source of abietane diterpenes with excellent antioxidant and antidiabetic activities that can be useful to modulate oxidative stress and might possibly be excellent candidates for the management of diabetes. This is the first scientific report on the phytochemical isolation and biological evaluation of the alpha-glucosidase and alpha-amylase inhibitory activities of Salvia aurita.

Cardiometabolic complications such as the metabolic syndrome and Type 2 Diabetes Mellitus (T2DM) are major causes of global morbidity and mortality. As sugar-sweetened beverages (SSBs) are implicated in this process, this study aimed to obtain greater mechanistic insights. Male Wistar rats (~200 g) were gavaged with a local SSB every day for a period of six months while the control group was gavaged with an iso-volumetric amount of water. Experimental dosages were calculated according to the surface area-to-volume ratio and were equivalent to 125 mL/day (in human terms). A proteomic analysis was performed on isolated liver samples and thereafter, markers of endoplasmic reticulum (ER) stress, antioxidant/oxidant capacity, calcium regulation, and mitochondrial functionality were assessed. These data show that SSB consumption resulted in (a) the induction of mild hepatic ER stress; (b) altered hepatic mitochondrial dynamics; and (c) perturbed calcium handling across mitochondria-associated ER membranes. Despite significant changes in markers of ER stress, the antioxidant response and calcium handling (proteomics data), the liver is able to initiate adaptive responses to counteract such stressors. However, the mitochondrial data showed increased fission and decreased fusion that may put the organism at risk for developing insulin resistance and T2DM in the longer term.

The re-investigation of a methanolic extract of Salvia africana-lutea collected from the Cape Floristic Region, South Africa (SA), afforded four new abietane diterpenes, namely 19-acetoxy-12-methoxycarnosic acid (1), 3β-acetoxy-7α-methoxyrosmanol (2), 19-acetoxy-7α-methoxyrosmanol (3), 19-acetoxy-12-methoxy carnosol (4), and two known named clinopodiolides A (5), and B (6), in addition to four known triterpenes, oleanolic, and ursolic acids (7, 8), 11,12-dehydroursolic acid lactone (9) and β-amyrin (10). The chemical structural elucidation of the isolated compounds was determined on the basis of one and two dimensional nuclear magnetic resonance (1D and 2D NMR), high-resolution mass spectrometry (HRMS), ultra violet (UV), fourier transform infrared (IR), in comparison with literature data. The in vitro bio-evaluation against alpha-glucosidase showed strong inhibitory activities of 8, 10, and 7, with the half inhibitory concentration (IC50) values of 11.3 ± 1.0, 17.1 ± 1.0 and 22.9 ± 2.0 µg/mL, respectively, while 7 demonstrated the strongest in vitro alpha-amylase inhibitory activity among the tested compounds with IC50 of 12.5 ± 0.7 µg/mL. Additionally, some of the compounds showed significant antioxidant capacities. In conclusion, the methanolic extract of S. africana-lutea is a rich source of terpenoids, especially abietane diterpenes, with strong antioxidant and anti-diabetic activities that can be helpful to modulate the redox status of the body and could therefore be an excellent candidate for the prevention of the development of diabetes, a disease where oxidase stress plays an important role.