Cucumber (Cucumis sativus L.) Fruit and Combination with Losartan Attenuate the Elevation of Blood Pressure in Hypertensive Rats Induced by Angiotensin II.

Objectives: Cucumis sativus L. (C. sativus) is vegetable commonly used for managing blood pressure and often consumed in combination with standard antihypertensive therapy, despite lack of scientific evidence supporting their use. Combination of herbs and standard medication could have positive or negative effects. Therefore, this study aimed to evaluate the antihypertensive activity of C. sativus and the combined effect with losartan in the hypertensive rat model induced by angiotensin II. Angiotensin II is a component of the renin-angiotensin-aldosterone system that, upon binding to its receptor, constricts blood vessels leading to elevation of blood pressure. Methods: In an antihypertensive study, rats received C. sativus orally at doses of 9, 18, 27, and 36 mg/kg (full dose); while in a combination study, animals received losartan 2.25 mg/kg combined by either with C. sativus 9 or 18 mg/kg. The standards group received losartan 2.25 mg/kg or 4.5 mg/kg (full dose). Results: Blood pressure was measured using the tail-cuff method. C. sativus significantly attenuated angiotensin II-induced hypertension as observed in groups receiving C. sativus at 9, 18, 27, and 36 mg/kg at 30 minutes after induction showed the average change (Δ) of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with respect to time zero were 28.8/18.3, 24.8/15.8, 22.8/15.5, and 11.5/9.0 mmHg, respectively. Whereas the average change (Δ) of SBP and DBP in the rats receiving the combination of half doses of C. sativus and losartan were 8.8/9.0 mmHg, respectively. These diminished effects were better than a full dose of C. sativus and comparable with a full dose of losartan (6.5/7.8 mmHg). Conclusion: The present findings indicate that C. sativus dose-dependently blocks blood pressure elevation induced by angiotensin II. The combination of half dose of C. sativus and losartan has an additive effect in lowering blood pressure.

Antihypertensive Activity of Combination of Anredera cordifolia (Ten.) V. Steenis and Sonchus arvensis L. Leaves on Epinephrine Induced Male Wistar Rat.

In Indonesia, hypertension is a condition that can lead to death through stroke and TB. Herbs have traditionally been used in Indonesia as an alternative medicine for lowering blood pressure. The leaves of Anredera cordifolia and Sonchus arvensis have been investigated for their antihypertensive potential. Based on the number of treatments, rats were randomized into groups. Each group consists of five rats. The test animals were grouping as follows: the positive control group (hypertension induction without treatment), A. cordifolia 50 mg/kg b.w. group, A. cordifolia 100 mg/kg b.w., S. arvensis 50 mg/kg b.w, S. arvensis 100 mg/kg b.w., A. cordifolia 25 mg/kg b.w + S. arvensis 25 mg/kg b.w, A. cordifolia 50 mg/kg b.w + S. arvensis 50 mg/kg b.w, and atenolol 4.5 mg/kg b.w. The rats were given 0.25 mg/kg b.w. of epinephrine intraperitoneally. The initial, after induction, and final blood pressure of the animals were measured using the CODA® noninvasive blood pressure device. All animal test groups at T60 showed a significant difference in systolic and diastolic blood pressures to initial blood pressure (T0), P < 0.05. The combination of A. cordifolia 50 mg/kg b.w and S. arvensis 50 mg/kg b.w showed the highest percent inhibition of systolic and diastolic blood pressure. The combination of A. cordifolia and S. arvensis 50-50 mg/kg b.w showed the best effect of lowering systolic and diastolic blood pressure on the pathway of inhibiting adrenergic receptors.

Molecular docking studies of α-mangostin, γ-mangostin, and xanthone on peroxisome proliferator-activated receptor gamma diphenyl peptidase-4 enzyme, and aldose reductase enzyme as an antidiabetic drug candidate.

α-mangostin, γ-mangostin, and xanthone are some of the marker compounds found in mangosteen (Garcinia mangostana Linn.) whose activity on several treatment targets including toward the peroxisome proliferator-activated receptor gamma (PPAR-γ) receptors, diphenyl peptidase 4 (DPP-4) enzyme, and aldose reductase enzyme is unknown. Although this plant has been predicted to be used as an alternative antidiabetic treatment, it has been proven through several previous studies. This research study used three natural ligands (α-mangostin, γ-mangostin, and xanthone) whose training set was designed using Molecular Operating Environment and then compared them with several drugs on the market that are used in the treatment of diabetes mellitus. The docking molecular results showed that the α-mangostin and γ-mangostin compounds had activity toward PPAR-γ receptor, DPP-4 enzyme, and aldose reductase enzyme by showing almost similar affinity values when compared to the comparison ligands. Meanwhile, xanthone showed unfavorable results. This approach shows that α-mangostin and γ-mangostin are predicted to play a role as antidiabetic mellitus in mangosteen when viewed from these mechanisms.

Regulation of mitogen-activated protein kinase signaling pathway and proinflammatory cytokines by ursolic acid in murine macrophages infected with Mycobacterium avium.

Mycobacterium avium, one of the closest relatives of Mycobacterium tuberculosis (MTB), offers an advantage in studying MTB because of its tuberculosis-like effect in humans and host immune tolerance. This study examined the antimycobacterial action of ursolic acid and its regulation in macrophages during infection. Colonyforming units of the bacteria were determined in the cell lysate of macrophages and in the supernatant. The effect of ursolic acid on macrophages during infection was determined by analyzing the phosphorylation of the mitogen-activated protein kinase signaling pathway and the concentrations of tumor necrosis factor-α, interleukin-1ß, interleukin-6, and nitrite. The colony-forming units analysis demonstrated that ursolic acid reduced the presence of Mycobacterium avium both intracellularly (in macrophages) and extracellularly. It decreased the levels of tumor necrosis factor- α and interleukin-6 but increased the concentrations of interleukin-1ß and nitrite during infection. It also inhibited the phosphorylation of ERK1/2 but phosphorylated the C-Jun N-terminal kinase signaling pathway. The antimycobacterial effect of ursolic acid correlated with its ability to regulate the activation of macrophages. This dual ability made the ursolic acid-related elimination of the mycobacteria more effective.

Combination Effect of Antituberculosis Drugs and Ethanolic Extract of Selected Medicinal Plants against Multi-Drug Resistant Mycobacterium tuberculosis Isolates.

Adverse drug reaction and resistance to antituberculosis drugs remain the causes of tuberculosis therapeutic failure. This research aimed to find the combination effect of standard antituberculosis drugs with Hibiscus sabdariffa L., Kaempferia galanga L., and Piper crocatum N.E. Br against multi-drug resistant (MDR) Mycobacterium tuberculosis isolates. Two MDR strains (i.e., isoniazid/ethambutol resistant and rifampicin/streptomycin resistant) of M. tuberculosis were inoculated in Löwenstein-Jensen medium containing a combination of standard antituberculosis drugs and ethanolic extracts of H. sabdariffa calyces, K. galanga rhizomes, and P. crocatum leaves using various concentration combinations of drug and extract. The colony numbers were observed for 8 weeks. The effect of the combination was analyzed using the proportion method which was calculated by the mean percentage of inhibition reduction in a number of colonies on drug-extract containing medium compared to extract-free control medium. The results showed that all three plant extracts achieved good combination effects with rifampicin against the rifampicin/streptomycin resistant strain. Antagonistic effects were, however, observed with streptomycin, ethambutol and isoniazid, therefore calling for caution when using these plants in combination with antituberculosis treatment.

Activity of Kaempferia pandurata (Roxb.) rhizome ethanol extract against MRSA, MRCNS, MSSA, Bacillus subtilis and Salmonella typhi.

Temu kunci (Kaempferia pandurata (Roxb.)) has a number of benefits and one of these is antibacterial. The rhizome is said to have antibacterial activity against Streptococcus mutans, Lactocillus sp. and Candida albicans. The aim of the study is to test the antibacterial activity of Kaempferia pandurata (Roxb.) rhizome ethanol extract on methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant coagulase negative Staphylococci (MRCNS), methicillin-sensitive Staphylococcus aureus (MSSA), Bacillus subtilis and Salmonella typhi. Antimicrobial activity of the extract was assayed by the microdilution method using Mueller Hinton Broth with sterilized 96 round-bottomed microwells to determine the Minimum Inhibitory Concentration (MIC) as well as to determine the time-kill activity. The MIC of the extract was 16 ppm for both Bacillus subtilis and MRSA; 8 ppm for both MSSA and Salmonella typhi and 4 ppm for MRCNS. Ethanol extract of Kaempferia pandurata (Roxb.) showed antibacterial activity against all the tested bacteria and was the most potent against MRCNS, with MIC 4 ppm. The killing profile test of the extract displayed bactericidal activity at 8-16 ppm against MRSA, MSSA, Bacillus subtilis and Salmonella typhi and bacteriostatic activity at 4 ppm towards MRCNS.

Toxicity studies of a bioactive protein with antithrombotic-thrombolytic activity, DLBS1033.

DLBS1033 is a bioactive protein extract containing Lumbricus rubellus and has been known to have antithrombotic/thrombolytic activity. The present study was aimed to assess the safety aspect of DLBS1033 in a preclinical setting, which included observation on toxic signs after acute and repeated administrations, and the drug's effect on prenatal development and drug interaction. In acute toxicity study, a high dose level (16.2 g/kg) of DLBS1033 was well tolerated. In subchronic toxicity study, after the doses of 270, 540 and 1080 mg/kg of DLBS1033 per day, no mortality was observed and other parameters were all observed to be normal. In prenatal developmental toxicity, no observed adverse effect level (NOAEL) of DLBS1033 was observed at a moderate dose (540 mg/kg). Coadministration of DLBS1033 with clopidogrel or aspirin did not cause gastric lesions, except when all three drugs were coadministrated. Taken together, results of the present study suggested that DLBS1033 is safe for long-term administration, with a caution at a high dose used during pregnancy, and can be used in combination with one of the antiplatelet drugs.