Natural Products Journal, The - Volume 12, Issue 5, 2022

Overexploitation of antibiotics has led to significant challenges with antimicrobial resistance. The gravity of this trend has resulted in the rapid emergence of multi-resistant pathogens. Increased frequency to treat infections and the unfeasibility to reverse this resistance have burdened researchers in developing novel mechanisms to counteract and obstruct antimicrobial resistance. An effective medical strategy to control resistance was to develop new and potent antibiotics although, a sobering reality is that the product pipeline towards new antibiotics is inadequate. To ensure continued effective treatment of bacterial infections, there is an urgent need to control as well as conserve existing antibiotics through novel approaches. Utilization of Essential Oils (EO) in a multi-target anti-infective therapy addresses this need by targeting the mechanism of bacterial resistance and discovering synergism between EO’s antimicrobial properties to anti-infectives. When introduced into a pharmaceutical formulation, this novel and rational approach will open the door towards the development of a new generation of antimicrobials. Today, several essential oils have the ability to act as resistant modifying agents and enhance the antimicrobial activity of anti-infectives. This review article intends to focus on the effectiveness of essential oils on drug-resistant pathogens, mechanisms to counteract antimicrobial resistance, approaches to enhance efficacy, and explore potential applications.

Podophyllotoxin is a nonalkaloid toxin aryltetralin lactone lignan, occurring naturally and extracted from the rhizomes and roots of Podophyllum species. Podophyllotoxin and its derivatives have been shown to possess a broad spectrum of pharmacological activities, mainly antineoplastic and antiviral properties. Podophyllotoxin serves as a potential anticancer agent and also the precursor for the chemical synthesis of some clinically important anticancer agents. The chemical modification and pharmacological investigation of podophyllotoxin derivatives have become a concern nowadays. Research interest has been stimulated towards the innovation of podophyllotoxin derivatives as the semi-synthetic anticancer agents, especially etoposide and teniposide. Podophyllotoxin and its derivatives are available in several formulations and also found to be effective in combination therapy. This review article aims to provide an overview of the role of podophyllotoxin, its mechanism of action, pharmacological activities, pharmacokinetics, available formulations, and its effects in combination therapy. This article also reviews the biosynthesis, structure and modifications of podophyllotoxin and its derivatives as an anticancer agent.

Background: Phaleria macrocarpa (Scheff.) Boerl. (Thymelaeaceae), usually referred to as God’s crown, Mahkota dewa, Pau, grows all year long in tropical countries, including Malaysia, Indonesia, Papua New Guinea, and Australia. It is traditionally used to treat haemorrhoids, stroke, heart disease, tumour, impotence, diabetes, allergies, kidney and liver disorders, migraine, acne, and skin ailments. Objective: The purpose of this systematic review is to provide important insight on P. macrocarpa’s traditional use, toxicity, classification of compounds, and pharmacological activities, thus identifying the gap in scientific analysis and potential analytical opportunities for future directions on this herb. Methods: The related data for this systematic review were collected from renowned online databases, namely Wiley Online Library, Web of Science, Springer Link, PubMed, Science Direct, Scopus, and Google scholar. Results: Around 48 compounds, including benzophenone, xanthonoids, norcucurbitacin derivatives, flavonoids, lignans, fatty acids and esters, phytosterols, aromatic acids, etc., were identified from different parts. These constituents and different solvent extracts using various identification techniques have been reported to show a broad range of pharmacological activities. Besides various traditional claims and pharmacological functions, scientific evidence on its ethnopharmacological aspects has been well-documented. Studies found that the plant demonstrates anti-diabetic, anti- oxidant, antimicrobial, anticancer, anti-hypercholesterolemia, and antihypertensive activities. Conclusion: Despite various claims, there is still inadequate scientific evidence, particularly on P. macrocarpa’s benefit in the management of dysentery, asthma, skin diseases, and rheumatoid arthritis, necessitating future studies. There is also a need to test its pharmacokinetics and toxicological data on humans to verify its potential bioactive properties.

Aim: The development of a suitable standardized Cyanthillium cinereum (L.) H.Rob. extract is an active ingredient in healthcare products. Background: C. cinereum is the herbal tea specified in the Thai National List of Essential (herbal) Medicines (NLEM) as the most efficacious tea for smoking cessation. However, herbal tea is inconvenient, and no standardized C. cinereum extraction method was known. Objectives: The study aims to develop a standardized C. cinereum extract preparation method and determine its biological activities. Methods: Various extraction and fractionation methods were performed in order to optimize a suitable standardized extract. The extraction yield, biological activities, and biomarkers (apigenin and luteolin) of the HPLC method were used to select the most suitable extraction method. Results: The results showed that the Microwave-Assisted Extraction (MAE) method with 75% EtOH was the most suitable method. The MAE method obtained apigenin and luteolin at 0.320±0.029 and 0.487±0.012 mg/g, respectively. MAE showed good anti-inflammatory and antioxidant (DPPH and FRAP assay) activities. Subsequently, the MAE extract was fractionated by the Diaion® HP-20 column in order to obtain the most suitable standardized extract. The 50% plus 75% EtOH fractions showed high apigenin (91.20±1.23 mg/g) and luteolin (167.00±0.49 mg/g) contents and exerted potent bioactivities. The standardized C. cinereum extract presented high effectiveness of NO inhibitory activity with an IC50 of 7.88±3.56 μg/mL, and also exerted DPPH scavenging efficacy with an IC50 value of 8.88±0.17 μg/mL and quercetin equivalent at 137.50±2.20 mg/g by FRAP assay. Conclusion: This study succeeded in developing a high-yield extraction method of standardized C. cinereum extract, with potent antioxidant and anti-inflammatory activities, suitable for various purposes.

Background: Depression is common in hypertensive patients, and monotherapy may contribute to controlling depression in hypertensive patients and improving socioeconomic outcomes. Previous studies have shown that Acacia tortilis possesses hypotensive activity. Objectives: The present study was planned to evaluate the hemodynamic activity and antidepressant effects of an ethanolic extract of Acacia tortilis leaves (ATEL) in salt-induced hypertensive rats. Methods: Sprague-Dawley rats were divided into 5 groups for experiments. The rats received respective treatment for 15 days: G1: Control (C); G2: hypertensive control (HC: high dietary salt, 4% 10ml/kg); G3-5: HC+ ATEL (50, 100, 150mg/kg respectively). Cardiac hemodynamics (mean arterial blood pressure: MAP and heart rate: HR) were measured in the anaesthetized rats by an invasive method. For this method, one carotid artery was catheterized, a pressure catheter (pressure- volume Millar microtip catheter connected to the Mikro-Tip Pressure-Volume System from Ultra Foundation Systems, PowerLab) was inserted, and the blood pressure (MAP in mm Hg) and HR (beats/min) were monitored continuously during the experiment. For the neuropharmacological studies, antidepressant activity was assessed by a forced swim test on the 15th day. Results: A dose-dependent significant increase in mobility time was observed in rats (G3-5) treated with HC + different doses of ATEL (p < 0.05). However, the mobility time was significantly reduced by HC (G2) treatment compared to the control (p< 0.05). The hypertensive control (high dietary salt: HC) group showed a significant increase in systolic blood pressure (SP), diastolic blood pressure (DP), MAP and HR (p<0.05) compared to the control (G1) group. At all doses (50, 100, and 150 mg/kg), MAP and HR were found to decrease significantly (p<0.05) compared to the values in the HC (G2) group. Further analysis revealed an improvement in heart rate variability (HRV) in ATEL-treated hypertensive rats. Conclusion: The present research suggests that increased dietary salt intake not only increases blood pressure significantly but also increases depression. ATEL contains some efficacious constituents, such as N, N-dimethyltryptamine (DMT: a 5-HT1A agonist), with predominant antidepressant and antihypertensive activity. Hence, ATEL appears to be a valuable plant extract that can be useful, at least as an adjunct, for therapy in patients who suffer from both depression and hypertension. Keywords: Ethanolic extract of Acacia.

Background: In recent years, the study of the structure and biological activity of medicinal plants has been particularly important to search for diabetes medicine. Ruellia tuberosa is used to treat various diseases such as diabetes by inhibiting the activity of α-glucosidase. Objective: In this study, an experiment was designed to isolatedisolate and identifiedidentifyα-glucosidase inhibitory extracts and compounds from Ruellia tuberosa L. through bio-assay guided isolation. Methods: Dry powder of Ruellia tuberosa L. was extracted with 70% ethanol, followed by liquidliquid partition with n-hexane, ethyl acetate and butanol, respectively. The extracts were evaluated withα-glucosidase inhibition. The potential extracts were isolated to identifynew compounds. The effects of these compounds on the α-glucosidase inhibitory were evaluated. Results: The a-glucosidase inhibitory activities showed that the n-hexane, ethyl acetate and the butanol extract had the α-glucosidase inhibition with an IC50 of 46.2 ± 0.9, 6.6 ± 2.9 and 8.9 ± 0.9 μg/mL, respectively. From the n-hexane and ethyl acetate extracts, the structures of four compounds were elucidated by NMR spectroscopic method, including lupeol (1), syringaresinol (2), apigenin (3), verbascoside (4). The α-glucosidase inhibitory activities showed that all isolated compounds were more active than the positive control - acarbose with an IC50 of 37.5 ± 0.4; 19.5 ± 0.2; 20.1 ± 0.3; 69.3 ± 0.2 μg/mL, respectively. Conclusion: The ethyl acetate extract showed strong activity about 19 times more than the positive control - acarbose. The compound syringaresinol (2) was the most powerful α-glucosidase inhibitor. Therefore, Ruellia tuberosa L. contains many compounds that can inhibit α-glucosidase activity.

Background: Ischemia/reperfusion (I/R) injury is one of the major causes of mortality. I/R injury leads to apoptosis in the brain, especially in the hippocampus and induces cognitive impairments. On the other hand, Salvia officinalis L. is perennial, evergreen subshrub that is widely used in traditional medicine. The antiapoptosis and antioxidant effects of Salvia officinalis L. have also been reported. Objective: In this study, we aimed to investigate the effect of Salvia officinalis L. on the expression of genes involved in apoptosis and percentage of viable neurons in the CA1 hippocampal region of rats following transient global I/R. Methods: The expression of Bcl-2, Bax, and Caspase 3 was evaluated using Real time PCR. Nissl staining was used to measure the number of viable neurons. The percentage of cell viability was also evaluated using MTT assay and flow cytometry. Salvia officinalis L. was injected intraperitoneal at the doses of 50, 75, and 100 mg/kg at both aqueous-alcoholic and aqueous extracts. Results: The expression of Bax and Caspase 3 was increased and the expression of Bcl-2 was decreased following transient global I/R in the CA1 region. The injection of Salvia officinalis L. at most doses reversed the effect of transient global I/R on genes expression. The number of viable neurons in the CA1 region was also decreased following transient global I/R and injection of Salvia officinalis L. at all doses reversed this effect. Conclusion: Transient global I/R significantly promotes apoptosis and cell death, and Salvia officinalis L. may induce neuroprotective and anti-apoptosis effects.

Background: Adenocarpus complicatus L. is one of Adenocarpus genus, which has about 50 species, from Fabaceae (Papilionaceae) family. This plant is found in the Mediterranean basin as a southern west part of Europe and North Afric forestes. Objective: Isolation of Isocarpine From Adenocarpus Complicatus as Anticandidal Agent. Methods: A new piperidine alkaloid Isocarpine was isolated from the aerial parts of Adenocarpus complicatus L., which is gross in Syria. The structure of the new compound was determined by UV, IR, EI-Ms, 1H-NMR, 13C-NMR, DEPT-135, DQF-COSY and HMQC. Results: The anticandidal activity of isocarpine was screened against 38 Candida strains and showed remarkable inhibitory effect compared with fluconazole as an antifungal reference drug. Conclusion: Isocarpine is antifungal agent.