Aedes aegypti and Aedes albopictus and Culex pipiens pallens mosquitoes transmit dengue fever and West Nile virus diseases, respectively. This study was conducted to determine the toxicity and mechanism of action of four flavonoids and two fatty acids from Millettia pinnata (Fabaceae) seed as well as six pure fatty acids and four fatty acid esters toward third instar larvae from insecticide-susceptible C. pipiens pallens and A. aegypti as well as wild A. albopictus. Efficacy of 12 experimental liquid formulations containing M. pinnata seed methanol extract and hydrodistillate (0.5–10.0% liquids) was also assessed. The contact toxicities of all compounds and 12 formulations were compared with those of two larvicides, temephos and fenthion and the commercial temephos 200 g/L emulsifiable concentrate (EC). The possible mode of larvicidal action of the constituents was elucidated using biochemical methods. Larval mortality and cAMP level were analyzed by the Bonferroni multiple-comparison method. Potent toxicity was produced by karanjin, oleic acid, karanjachromene, linoleic acid, linolenic acid, pongamol, pongarotene, and elaidic acid toward C. pipiens pallens larvae (24 h LC50, 14.61–28.22 mg/L) and A. aegypti larvae (16.13–37.61 mg/L). Against wild A. albopictus larvae, oleic acid (LC50, 18.79 mg/L) and karanjin (35.26 mg/L) exhibited potent toxicity. All constituents were less toxic than either temephos or fenthion. Structure–activity relationship indicates that the degree of saturation, the side chain length, and the geometric isomerism of fatty acids appear to play a role in determining the fatty acid toxicity. Acetylcholinesterase (AChE) is the main site of action of the flavonoids, oleic acid, and palmitic acid. The mechanism of larvicidal action of elaidic acid, arachidic acid, and behenic acid might be due to interference with the octopaminergic system. Linoleic acid and linolenic acid might act on both AChE and octopaminergic receptor. M. pinnata seed extract or hydrodistillate applied as 10% liquid provided 100% mortality toward the three mosquito species larvae and the efficacy of the liquids was comparable to that of temephos 200 g/L EC. Further studies will warrant possible applications of M. pinnata seed-derived products as potential larvicides for the control of mosquito populations.

Moringa oleifera is one of the popular functional foods that has been tremendously exploited for synthesis of a vast majority of metal nanoparticles (NPs). The diverse secondary metabolites present in this plant turn it into a green tool for synthesis of different NPs with various biological activities. In this review, we discussed different types of NPs including silver, gold, titanium oxide, iron oxide, and zinc oxide NPs produced from the extract of different parts of M. oleifera. Different parts of M. oleifera take a role as the reducing, stabilizing, capping agent, and depending on the source of extract, the color of solution changes within NP synthesis. We highlighted the role of polyphenols in the synthesis of NPs among major constituents of M. oleifera extract. The different synthesis methods that could lead to the formation of various sizes and shapes of NPs and play crucial role in biomedical application were critically discussed. We further debated the mechanism of interaction of NPs with various sizes and shapes with the cells, and further their clearance from the body. The application of NPs made from M. oleifera extract as anticancer, antimicrobial, wound healing, and water treatment agent were also discussed. Small NPs show better antimicrobial activity, while they can be easily cleared from the body through the kidney. In contrast, large NPs are taken by the mono nuclear phagocyte system (MPS) cells. In case of shape, the NPs with spherical shape penetrate into the bacteria, and show stronger antibacterial activity compared to the NPs with other shapes. Finally, this review aims to correlate the key characteristics of NPs made from M. oleifera extract, such as size and shape, to their interactions with the cells for designing and engineering them for bio-applications and especially for therapeutic purposes. Graphical Abstract

Propolis (or bee glue), collected from botanical sources by honey bee, has been used as a popular natural remedies in folk medicine throughout the world. This study was conducted to assess growth inhibitory effects of ethanol extracts of propolis (EEPs) from 20 different regions in South Korea on human intestinal bacteria as well as their human β-amyloid precursor cleavage enzyme (BACE-1), acetylcholinesterase (AChE) inhibitory, antioxidant, antiproliferative, and anti-human rhinovirus activities. The Bonferroni multiple-comparison method was used to test for significant differences in total polyphenol and flavonoid contents among EEP samples using SAS 9.13 program. Correlation coefficient (r) analysis of the biological activities of EEP samples was determined using their 50 % inhibition concentration or minimal inhibitory concentration values and their polyphenol or flavonoid contents in 20 native Korean EEP samples. The amounts of total polyphenol and flavonoids in the Korean EEP samples ranged from 49 to 239 mg gallic acid equivalent (GAE)/g EEP (Brazilian, Chinese, and Australian samples, 127–142 mg GAE/g EEP) and from 21 to 50 mg quercetin equivalent (QE)/g EEP (Brazilian, Chinese, and Australian samples, 33–53 mg QE/g EEP), respectively. Correlation coefficient analysis showed that total polyphenol contents may be negatively correlated with 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity (r = −0.872) and total flavonoid content has no correlation with the activity (r = 0.071). No direct correlation between BACE-1 inhibition, AChE inhibition, or antiproliferative activity and total polyphenol or total flavonoid content in Korean EEP samples was found. Gram-positive and Gram-negative bacteria were observed to have different degrees of antimicrobial susceptibility to the EEP samples examined, although ciprofloxacin susceptibility among the bacterial groups did not differ greatly. Further studies will warrant possible applications of propolis as potential therapeutic BACE-1 blocker, antioxidant, antiproliferative agent, and antimicrobial agent.

Origanum vulgare commonly known as oregano belongs to mint family (Laminaceae), and native to temperate western and mediterranean region. In our present study, we have identified the bio-active principles of oregano essential oil (EO) and evaluated its apoptotic effects against human stomach cancer cell lines (AGS). The EO altered colony forming characteristics of cancer cell, migration ability of cancer cell and thus prevented cancer cell proliferation. Furthermore, to evaluate the molecular mechanism involved in cancer cell death, we studied the genes that are involved in fatty acid and cholesterol biosynthesis pathway including 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), Acetyl CoA synthase (ACC), sterol regulatory element-binding protein (SPREPB1) and fatty acid synthase (FASN) respectively. The pathway genes such as HMGCR, ACC, SPREPB1 and FASN decreased in transcript profile and protein accumulation resulting in the inhibition of cell growth. The increase of BAX expression and downregulation of BCL2 expression indicated that oregano EO induced mitochondrial mediated apoptosis. In addition, the cancer cell undergone apoptosis was also confirmed by Hoechst, PI staining and DNA fragmentation. The present study finds rationale to use the oregano EO for stomach cancer treatments in traditional medicinal practice.

The isomers of citral (cis‐citral and trans‐citral) were isolated from the Cymbopogon citratus (DC.) Stapf oil demonstrates many therapeutic properties including anticancer properties. However, the effects of citral on suppressing human prostate cancer and its underlying molecular mechanism have yet to be elucidated. The citral was isolated from lemongrass oil using various spectroscopic analyses, such as electron ionized mass spectrometry (EI‐MS) and nuclear magnetic resonance (NMR) spectroscopy respectively. We carried out 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay to evaluate the cell viability of citral in prostate cancer cells (PC‐3 and PC3M). Furthermore, to confirm that PC3 undergoes apoptosis by inhibiting lipogenesis, we used several detection methods including flow cytometry, DNA fragmentation, Hoechst staining, PI staining, oil staining, qPCR, and Western blotting. Citral impaired the clonogenic property of the cancer cells and altered the morphology of cancer cells. Molecular interaction studies and the PASS biological program predicted that citral isomers tend to interact with proteins involved in lipogenesis and the apoptosis pathway. Furthermore, citral suppressed lipogenesis of prostate cancer cells through the activation of AMPK phosphorylation and downregulation of fatty acid synthase (FASN), acetyl coA carboxylase (ACC), 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGR), and sterol regulatory element‐binding protein (SREBP1) and apoptosis of PC3 cells by upregulating BAX and downregulating Bcl-2 expression. In addition, in silico studies such as ADMET predicted that citral can be used as a safe potent drug for the treatment of prostate cancer. Our results indicate that citral may serve as a potential candidate against human prostate cancer and warrants in vivo studies.