A comprehensive review on Cosmos caudatus (ulam raja): pharmacology, ethnopharmacology, and phytochemistry

Cosmos caudatus or Ulam Raja in Malay originated from Latin America and transferred to Europe, Africa, and tropical Asia. It has been known for many traditional practices worldwide such as to rigidify bones and tone up blood circulation. The aim of this review is to summarize and discuss the association between phytochemical and pharmacological reports of C. caudatus and their traditional uses via ethnopharmacological approaches. Cosmos caudatus is a traditional medicinal plant used widely for culinary and therapeutic purposes. Phytochemical studies indicated the presence of Phenolic acids, flavonoids, tannins, sesquiterpene lactones, carbohydrates, minerals and vitamins in leaves while phenylpropanoids were in roots. Pharmacological data have been compiled for diverse activities for fresh leaves and extracts such as antihypertensive, antihyperlipidemic, antidiabetic, antimicrobial, antioxidant and antiosteoporotic. These activities experimented by in vitro and in vivo studies. Multiple C. caudatus constituents propose many potential actions in different fields such as neuroprotection, antidepression, and gastroprotection

Potential of Calcium Carbonate Nanoparticles for Therapeutic Applications

The application of nanoparticles (NPs) has attracted considerable attention as targeted delivery systems. CaCO3 has become the focus due to its advantages including affordability, low toxicity, biocompatibility, cytocompatibility, pH sensitivity and sedate biodegradability and environment friendly materials. In this article, we will discuss the potential roles of CaCO3 -NPs in three major therapeutic applications; as antimicrobial, for drug delivery, and as gene delivery nanocarrier

Cosmos caudatus extract/fractions reduce smooth muscle cells migration and invasion in vitro: a potential benefit of suppressing atherosclerosis

Background: Cosmos caudatus Kunth is a medicinal herb used traditionally in Latin America and South East Asia to retard aging, rigidify bones and for several cardiovascular uses. Objective: Is to assess C. caudatus extract/fractions’ antioxidant and vascular smooth muscle cells (VSMC) migration and invasion inhibition capacity in vitro. Methods: Cosmos caudatus shoots were extracted by cold maceration in 50% ethanol to produce crude (CEE), and then the extract was fractionated to butanol (Bu.F), and aqueous fractions (Aq.f). Phenolics and saponins were quantified in extract and fractions by colorimetric methods and their antioxidant capacity was assayed in four different tests. Cytotoxic effect and safety level concentrations were determined for the fractions by using MTT assay. Migration and invasion inhibitory potential were measured in vitro at three different concentrations equivalent to (IC10, IC25, and IC50). Finally, invasion inhibitory index was calculated to obtain the best fraction(s) that show(s) the highest ratio of cell invasion inhibition to the total cell migration inhibition. Results: Butanol fraction yield was the lowest; nevertheless, its phytochemical contents, antioxidant activities as well as its potency were the highest. Unlike other fractions, Bu.F was strongly correlated with all antioxidant assays experimented. In addition, it has the highest inhibitory effect at IC25 against VSMCs migration and invasion that accounts for 53.93% and 59.94% respectively. Unexpectedly, Bu.F and CEE at IC10 displayed the highest invasion inhibitory index (approx. 68%). Conclusion: Butanol fraction of C. caudatus offers a potentiality for the discovery of new leads for preventing atherosclerosis

Evaluation of potential bacterial protease inhibitor properties of selected hydroxyquinoline derivatives : An in silico docking and molecular dynamics simulation approach

Antimicrobial drug resistance (AMR) is a severe global threat to public health. The increasing emergence of drug-resistant bacteria requires the discovery of novel antibacterial agents. Quinoline derivatives have previously been reported to exhibit antimalarial, antiviral, antitumor, antiulcer, antioxidant and, most interestingly, antibacterial properties. In this study, we evaluated the binding affinity of three newly designed hydroxyquinolines derived from sulfanilamide (1), 4-amino benzoic acid (2) and sulfanilic acid (3) towards five bacterial protein targets (PDB ID: 1JIJ, 3VOB, 1ZI0, 6F86, 4CJN). The three derivatives were designed considering the amino acid residues identified at the active site of each protein involved in the binding of each co-crystallized ligand and drug-likeness properties. The ligands displayed binding energy values with the target proteins ranging from −2.17 to −8.45 kcal/mol. Compounds (1) and (3) showed the best binding scores towards 1ZI0/3VOB and 1JIJ/4CJN, respectively, which may serve as new antibiotic scaffolds. Our in silico results suggest that sulfanilamide (1) or sulfanilic acid (3) hydroxyquinoline derivatives have the potential to be developed as bacterial inhibitors, particularly MRSA inhibitors. But before that, it must go through the proper preclinical and clinical trials for further scientific validation. Further experimental studies are warranted to explore the antibacterial potential of these compounds through preclinical and clinical studies. Communicated by Ramaswamy H. Sarma

Pharmacotherapeutics applications and chemistry of chalcone derivatives

Chalcones have been well examined in the extant literature and demonstrated antibacterial, antifungal, anti-inflammatory, and anticancer properties. A detailed evaluation of the purported health benefits of chalcone and its derivatives, including molecular mechanisms of pharmacological activities, can be further explored. Therefore, this review aimed to describe the main characteristics of chalcone and its derivatives, including their method synthesis and pharmacotherapeutics applications with molecular mechanisms. The presence of the reactive α,β-unsaturated system in the chalcone’s rings showed different potential pharmacological properties, including inhibitory activity on enzymes, anticancer, anti-inflammatory, antibacterial, antifungal, antimalarial, antiprotozoal, and anti-filarial activity. Changing the structure by adding substituent groups to the aromatic ring can increase potency, reduce toxicity, and broaden pharmacological action. This report also summarized the potential health benefits of chalcone derivatives, particularly antimicrobial activity. We found that several chalcone compounds can inhibit diverse targets of antibiotic-resistance development pathways; therefore, they overcome resistance, and bacteria become susceptible to antibacterial compounds. A few chalcone compounds were more active than conventional antibiotics, like vancomycin and tetracycline. On another note, a series of pyran-fused chalcones and trichalcones can block the NF-B signaling complement system implicated in inflammation, and several compounds demonstrated more potent lipoxygenase inhibition than NSAIDs, such as indomethacin. This report integrated discussion from the domains of medicinal chemistry, organic synthesis, and diverse pharmacological applications, particularly for the development of new anti-infective agents that could be a useful reference for pharmaceutical scientists

Natural products as novel anti-obesity agents: insights into mechanisms of action and potential for therapeutic management

Obesity affects more than 10% of the adult population globally. Despite the introduction of diverse medications aimed at combating fat accumulation and obesity, a significant number of these pharmaceutical interventions are linked to substantial occurrences of severe adverse events, occasionally leading to their withdrawal from the market. Natural products serve as attractive sources for anti-obesity agents as many of them can alter the host metabolic processes and maintain glucose homeostasis via metabolic and thermogenic stimulation, appetite regulation, pancreatic lipase and amylase inhibition, insulin sensitivity enhancing, adipogenesis inhibition and adipocyte apoptosis induction. In this review, we shed light on the biological processes that control energy balance and thermogenesis as well as metabolic pathways in white adipose tissue browning, we also highlight the anti-obesity potential of natural products with their mechanism of action. Based on previous findings, the crucial proteins and molecular pathways involved in adipose tissue browning and lipolysis induction are uncoupling protein-1, PR domain containing 16, and peroxisome proliferator-activated receptor-γ in addition to Sirtuin-1 and AMP-activated protein kinase pathway. Given that some phytochemicals can also lower proinflammatory substances like TNF-α, IL-6, and IL-1 secreted from adipose tissue and change the production of adipokines like leptin and adiponectin, which are important regulators of body weight, natural products represent a treasure trove for anti-obesity agents. In conclusion, conducting comprehensive research on natural products holds the potential to accelerate the development of an improved obesity management strategy characterized by heightened efficacy and reduced incidence of side effects

In vitro antioxidant and anti-atherosclerotic activities of phenolic saponin rich fraction of Cosmos caudatus kunth

Cosmos caudatus or Ulam raja as it is known in Malaysia, is a tropical plant that has been known in South East Asia for many traditional uses, some were proved by pharmacological studies, while others yet to be validated. In this study, we are inspecting the atheroprotective effects for ulam raja extract/fractions through in vitro. The shoot samples were collected fresh from the plant stem, oven dried and grinded. A 100 gm sample was macerated in 50% (v/v) ethanol, twice for 48hours each time with intermittent shaking, after extract pooling, solvent was removed under reduced pressure and lyophilized to produce the crude extract. Subsequently, the crude extract was fractionated to produce the butanol and the aqueous fractions. In order to determine the phenolic, saponin and steroidal saponin contents, we employed folinciocalteu, vanillin-sulfuric acid and anisaldehyde-sulfuric acid methods respectively. Butanol fraction was the phenolic-saponin rich fraction (PSRF) due to the fact that it possesses the richest total phenolic, saponin and steroidal saponin contents (88.45 mg GAE/g DW, 64.23 and 23.3 mg DE/g DW) respectively (P<0.05), compared to the other C. caudatus derived fractions. Similarly, butanol fraction showed the highest antioxidant activity in four assays namely, DPPH, ABTS, iron chelating and BCB activity assays. Antioxidant activities for butanol fraction were (72.65 mg TEAC/ g DW), (94.47 mg TEAC/ g DW), (16.03 mg EDTA/ g DW) and (19.43 mg TEAC/ g DW) respectively. Cytotoxic effects of crude, butanol and aqueous fractions were determined by MTT assay in rat aortic smooth muscle cell line (A-10) for 24 hours, and IC50 were as follows 460.78, 313.96 and 949.2 μg/mL respectively. IC50 for the three fractions was going in the same trend of the previous assays, as butanol was the most potent, followed by crude, and lastly the aqueous fraction. Three concentrations (IC10, IC25 and IC50) of the three fractions were used to treat A-10 cell line to assess their activities in inhibiting migration and invasion of cells using Boyden chamber assay. Butanol fraction Intermediate concentration (IC25) demonstrated the strongest activity to inhibit smooth muscle cells from migration and invasion in in vitro assays, as they were reduced by 53.93% and 59.94% respectively compared to untreated control cells. However, the invasion inhibition index referred to that butanol and crude mild concentrations (IC10) showed the highest index value ~68%, which means the best cell invasion to cell migration inhibition in vitro. Taken together, results strongly support that PSRF from C. caudatus can be used to reduce atherosclerotic plaque formation by reducing its key mechanism represented by SMCs migration and invasion, and its subsequent events such as myocardial infarction and strokes. This can be attributed to the high contents of phenolics, saponins and vitamins, and their ability to reduce the oxidative stress and free radicals, in addition to the other mechanism of action of other flavonoids

Insights into the computer-aided drug design and discovery based on anthraquinone scaffold for cancer treatment: A protocol for systematic review

There is still unmet medical need in cancer treatment mainly due to drug resistance and adverse drug events. Therefore, the search for better drugs is essential. Computer-aided drug design (CADD) and discovery tools are useful to streamline the lengthy and costly drug development process. Anthraquinones are a group of naturally occurring compounds with unique scaffold that exert various biological properties including anticancer activities. This protocol describes a systematic review that provide insights into the computer-aided drug design and discovery based on anthraquinone scaffold for cancer treatment. It was prepared in accordance with the "Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 guidelines, and published in the "International prospective register of systematic reviews" database (PROSPERO: CRD42023432904). Search strategies will be developed based on the combination of relevant keywords and executed in PubMed, Scopus, Web of Science and MedRxiv. Only original studies that employed CADD as primary tool in virtual screening for the purpose of designing or discovering anti-cancer drugs involving anthraquinone scaffold published in English language will be included. Two independent reviewers will be involved to screen and select the papers, extract the data and assess the risk of bias. Apart from exploring the trends and types of CADD methods used, the target proteins of these compounds in cancer treatment will also be revealed in this review. It is believed that the outcome of this study could be utilized to support the ongoing research in similar area with better quality and greater probability of success, consequently optimizing the resources in subsequent in vitro, in vivo, non-clinical and clinical development. It will also serve as an evidence based scientific guide for new research to design novel anthraquinone-derived drug with improved efficacy and safety profile for cancer treatment

Renal ultrastructural alterations induced by various preparations of mefenamic acid

Mefenamic acid (MFA) treatment is associated with a number of cellular effects that potentiate the incidence of renal toxicity. The aim of this study is to investigate the potential ultrastructural alterations induced by various preparations of MFA (free MFA, MFA-Tween 80 liposomes, and MFA-DDC liposomes) on the renal tissues. Sprague-Dawley rats were subjected to a daily dose of MFA preparations for 28 days. Renal biopsies from all groups of rats under study were processed for transmission electron microscopic examination. The findings revealed that MFA preparations induced various ultrastructural alterations including mitochondrial injury, nuclear and lysosomal alterations, tubular cells steatosis, apoptotic activity, autophagy, and nucleophagy. These alterations were more clear in rats received free MFA, and MFA-Tween 80 liposomes than those received MFA-DDC liposomes. It is concluded that MFA-DDC liposomes are less potential to induce renal damage than free MFA and MFA-Tween 80 liposomes. Thus, MFA-DDC liposomes may offer an advantage of safe drug delivery

Evaluating NSAIDs in SARS-CoV-2: Immunomodulatory mechanisms and future therapeutic strategies

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely recognized for their analgesic and anti-inflammatory properties. Amidst the SARS-CoV-2 pandemic, the role of NSAIDs in modulating viral and bacterial infections has become a critical area of research, sparking debates and necessitating a thorough review. This review examines the multifaceted interactions between NSAIDs, immune responses, and infections. Focusing on the immunomodulatory mechanisms of NSAIDs in SARS-CoV-2 and their implications for other viral and bacterial infections, we aim to provide clarity and direction for future therapeutic strategies. NSAIDs demonstrate a dual role in infectious diseases. They reduce inflammation by decreasing neutrophil recruitment and cytokine release, yet potentially compromise antiviral defense mechanisms. They also modulate cytokine storms in SARS-CoV-2 and exhibit the potential to enhance anti-tumor immunity by inhibiting tumor-induced COX-2/PGE2 signaling. Specific NSAIDs have shown efficacy in inhibiting viral replication. The review highlights NSAIDs' synergy with other medications, like COX inhibitors and immunotherapy agents, in augmenting therapeutic effects. Notably, the World Health Organization's analysis found no substantial link between NSAIDs and the worsening of viral respiratory infections. The findings underscore NSAIDs' complex role in infection management. Understanding these interactions is crucial for optimizing therapeutic approaches in current and future pandemics. However, their dual nature warrants cautious application, particularly in vulnerable populations. NSAIDs present a paradoxical impact on immune responses in viral and bacterial infections. While offering potential benefits, their usage in infectious diseases, especially SARS-CoV-2, demands a nuanced understanding to balance therapeutic advantages against possible adverse effects