Pharmacological Research - Natural Products最新文献

Terminalia chebula Retz. is an extensively used plant for the treatment of numerous ailments in Ayurveda. The major phytochemicals found in this plant are tannins, phenols which possess anti-inflammatory, anti-oxidative, anti-carcinogenic, and anti-mutagenic effect. In the present study, we focused on identification of drug like candidates and exosomes mediated drug delivery system for cancer treatment. We have investigated phenolic content, anti-inflammatory potential, and anti-oxidative capacity of hydro-alcoholic Terminalia chebula Retz. fruit extract (TCE) which was found higher when compared to the standards. HPLC and GC-MS analysis have revealed the presence of 73 compounds in TCE and three of them were further exploited for the development of novel safer and potent anticancer drug. Using computational approach the potential inhibitory effects and binding of 3 phytochemicals (i.e., chebulagic acid, chebulinic acid and corilagin) obtained from TCE against 8 structural and functional target proteins (i.e., IL-6, NFκβ, LRP-6, BCL-XL, MEK1, Aurora kinase, EGFR, and α₁β₂) that are crucially involved in carcinogenesis were studied. Chebulagic acid has showed good docking score with almost all the protein considered in this study. We have observed higher binding affinity of chebulagic acid for the target proteins as evidenced from the more negative value of the binding energy compared to other ligands i.e. chebulinic acid and corilagin by docking analysis. Chebulagic acid forms five and four hydrogen bonds with amino acids in the active site of the IL-6 and NFκβ target protein, with the least binding energy of −10.79 and −10.26 respectively and hence considered as an excellently docked conformation. Exosome mediated TCE delivery was investigated in HuH-7 cell line. The in-vitro cytotoxic study by MTT assay and apoptotic study in HuH-7 cell lines have revealed that TCE has anti-proliferative activity in malignancy like hepatocellular carcinoma, however TCE loaded in exosomes (Ex-TCE) showed better results due to increased intracellular delivery of TCE.

The mechanisms of action of traditional herbal medicines are being actively researched, but little information is available regarding the interactions of these agents with concomitant drugs; clarifying these interactions is extremely important for the appropriate and safe use of these agents. Changes in the expression of drug-metabolizing enzymes are essential for determining drug-drug interactions. In this study, we investigated the effects of traditional herbal medicine on the expression and activity of cytochrome P450 (Cyp), a drug-metabolizing enzyme. This study focused on Tokishakuyakusan (TSS), Keishibukuryogan (KBG), and Kamishoyosan (KSS), which are effective for treating symptoms unique to women. Female mice were given normal chow or chow containing TSS, KBG, or KSS for four weeks. The mRNA levels of Cyp in the liver and small intestine were analyzed, and the Cyp3a protein level and metabolic activity were also evaluated. No significant differences in the mRNA expression levels of Cyp isozymes in the liver and small intestine were detected between the TSS-treated group and the control group. The protein expression level and metabolic activity of Cyp3a, which is the most important enzyme for drug metabolism, were not affected by TSS administration. In addition, no changes in the expression level and metabolic activity of Cyp in the liver and small intestine were detected in mice who were fed KBG or KSS. The results of this study revealed that TSS, KBG, and KSS do not affect Cyp expression and activity. Therefore, these herbal medicines are unlikely to interact with Cyp substrate drugs.

Introduction

Endophytes are considered preeminent candidates for novel drug discovery as they possess a wide variety of bioactive compounds. The diversity, biological activities, and metabolites produced by endophytes associated with Curcuma have been studied for the last few years. Therefore, the present review aims to draw attention to the bioactive metabolites produced by endophytes associated with Curcuma species and their significance in the pharmaceutical sector.

Method

The literature investigation was carried out through various databases such as Scopus, Web of Science, PubMed, Elsevier Science Direct, ResearchGate, and Google Scholar. The taxonomic data was validated through “The World Flora Online”, “Medicinal Plant Names Services”, “Plants of the World Online”, and “The Plant List”.

Results

This literature study revealed that amongst Curcuma species, only 11 species have been studied in the context of endophytes so far. Overall, a total number of 42 endophyte-derived metabolites exhibited various biological activities with anticancer, antimicrobial, antioxidant, and anti-inflammatory properties, and many more were encountered. The reported compounds belong to different chemical classes such as alkaloids, phenolics, terpenoids, steroids, polyketides, and other compounds.

Conclusion

This review evidenced Curcuma colonized endophytes as a source of pharmaceutically significant metabolites. This compiled data could act as a source of information on potent endophytes and their bioactive metabolites reported from Curcuma and pave the way for future investigations.

Cardiovascular conditions such as coronary artery disease, stroke, vascular disease, and heart failure are made more likely to occur by hypertension. Hypertension doesn't typically present with symptoms until it has progressed, but it can cause serious, lifelong health problems. The cost of and potential side effects from antihypertensive drugs are concerns. As a result, in the current environment, it is essential to investigate the therapeutic potential of herbal medications with minimal side effects. It is well known that Nigella sativa and its active components, including thymoquinone, thymol, and nigericin, are potential phytomedicines with anti-inflammatory, hypotensive, calcium channel blocker, and diuretic properties that significantly lower blood pressure. This review covers the pharmacological effects, chemical composition, and antihypertensive qualities of N. sativa, with an emphasis on the health benefits and nanoformulations of thimoquinone. Moreover, a variety of nanotechnological formulations are employed to encapsulate thymoquinone. This review further provided the effectiveness of nanoparticles in lowering blood pressure and suggests combining them with N. sativa or thymoquinone to increase their antihypertensive effects.This study concluded the potential of N. sativa as a antihypertensive agent. Thimoquinone, a major component in N. sativa is extensively studied and nanofromulated bioactive compound that can be used in many agri-food-pharma industries.

Citrus jambhiri (Lush) and paradisi (Macf.) have wide usage as food spices. Therefore, the presence of profiled phytochemicals, the antioxidant, antimicrobial and anti-plasmodial activities of the stem and fruit-peel extracts were studied. The citrus stem and fruit-peel extracts were analyzed using ultra-high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-qTOF/MS) and anti-plasmodial activities against chloroquine-sensitive (CQS) strain of Plasmodium falciparum, antimicrobial against Gram-positive and Gram-negative bacterial strains as well as antioxidant potentials were determined in triplicate. Metabolite fingerprinting of C. jambhiri stem and C. paradisi fruit-peel extracts revealed rutamarin and spicatin respectively. The stem and fruit-peel of C. jambhiri showed moderate antimalarial activity. C. paradisi stem revealed a weak activity; however, C. paradisi fruit-peel showed no antimalarial activity (IC₅₀ >100 μg/mL). C. paradisi and C. jambhiri extracts exhibited lower inhibition concentration (IC₅₀: 3.0–7.0 µgmL⁻¹), than ascorbic acid (IC₅₀: 9.0 µgmL⁻¹). C. paradisi stem DCM/methanol extract showed a reducing value of EC₅₀: 8.00 µgmL⁻¹ whereas reference compound used, (ascorbic acid) had EC₅₀: 11.00 µgmL⁻¹. Furthermore, C. jambhiri stem extract showed the best antimicrobial activity against the clinical isolates with high inhibition zones ≥ 15 mm. There is a paucity of information on the identification and importance of rutamarin and spicatin from Citrus extracts as a functional food ingredient with a promising compound implicated in the development of antimalarial drugs. Overall result however showed that the two citrus plants contain antioxidant constituents whereas C. jambhiri could be important source of antimicrobial agents. The study profiled two new compounds from the citrus extract and showed the potentials of the plant as source of antimalaria drug.

There has been increasing effort in the research and development of dopamine neurotransmission as an early clinical marker for neurodegenerative diseases, namely Parkinson’s and Alzheimer’s disease in recent years. Given the side effects and clinical performances of some approved dopaminergic drugs, there is a growing interest in exploring the neuroprotective properties of medicinal plants as alternatives. Although not curative, these phytochemical compounds show potential in protecting and maintaining the integrity and functions of dopaminergic neurons, thereby mitigating neurological symptoms. This review highlights medicinal plants and their bioactive compounds with neuroprotective effects on the dopaminergic system of the human brain, particularly focussing on their mechanism of actions, potentials and challenges as alternative therapeutics.

Ethnopharmacology relevance: Liver problems are severe risks to human health and the most significant cause of death worldwide. For decades, the efficient treatment of hepatic disorders has been achieved through various herbal formulations and traditional Chinese medicine (TCM). Network pharmacology has been employed to develop drug-target-disease networks and to study the active phytoconstituents and multi-target action mechanisms for these formulations.

Aim

To summarize the recent application status of network pharmacology in the treatment of hepatic disorder through a literature review and to review the related databases, plant compounds, traditional herbal formulation, and their mechanism of action for combating hepatic disorder.

Materials and methods

In this review, literature was searched in PubMed, ScienceDirect, and Google Scholar using the keywords “liver disorder’, “hepatoprotective formulation,” “traditional Chinese medicine,” “herbal medicine,” and “network pharmacology” from 1995 to 2023.

Results

This review presents current research on various herbal formulations, including traditional Chinese medicinal formulas and other plant extracts, with an emphasis on the utilization of plant bioactive chemicals, predicted targets, mechanism of action, and their anticipated signal pathways in the treatment of hepatic disorders. It also summarizes the relevant databases and application of network pharmacology in hepatology.

Conclusions

This article offers details on a recent study using the network pharmacology technique, which will not only give a new research paradigm for natural products but also improve hepatoprotective drug development strategies.

Background

Epilepsy, a prevalent neurological disorder affecting individuals across all age groups, often requires treatment with antiepileptic drugs (AEDs). While Carbamazepine (CBZ) serves a commonly prescribed first-line medication, its efficacy is limited in 30–40 % of patients. In exploring alternative treatment options. Herbal medicines like Withania somnifera (W. somnifera) offer promising benefits with reduced adverse effects. This study aims to assess the therapeutic impacts of W. somnifera and CBZ on behavioral paralysis, reproductive abilities, and lifespan in a Drosophila paralytic temperature-sensitive mutant (para^ST76).

Methods

para^ST76 flies were exposed to three distinct concentrations of W. somnifera or CBZ added to wheat flour-agar media.

Results

The results indicate that high concentration of W. somnifera effectively extended the lifespan of Drosophila para^ST76 without compromising fecundity and fertility. Conversely, exposure to 40 μg/ml of CBZ resulted in a shortened lifespan and decreased reproductive ability in the para^ST76 mutant. Importantly, our findings demonstrate that neither W. somnifera nor CBZ exerted any notable impact on behavioral paralysis, as per our dataset analysis.

Conclusion

This study exhibits that W. somnifera is a safe compound, devoid of any adverse effects, and possesses the capability to prolong the lifespan of Drosophila. Nevertheless, it does not affect the voltage-gated sodium channel of the para^ST76 mutant.

Resveratrol, a natural polyphenol found in various plants, has garnered significant attention for its potential health benefits. With the global rise in chronic diseases, including cancer, cardiovascular issues, and diabetes, there is a growing interest in alternative interventions. Resveratrol, known for its antiangiogenic, immunomodulatory, antimicrobial, and neuroprotective properties, has shown promise in laboratory studies for preventing chronic diseases and extending lifespan. Despite the challenges of implementing caloric restriction in real-life situations, resveratrol has emerged as a potential alternative. Found in foods like red grapes, berries, peanuts, and dark chocolate, resveratrol exhibits diverse effects on apoptosis, oxidative stress, inflammation. It addresses various pathways, including NF-kB and PI3K/Akt, making it a candidate for conditions like cardiovascular disease, diabetes, and cancer. Clinical trials have explored resveratrol's safety, suggesting doses of up to 5 g per day are generally well-tolerated. However, its effectiveness can be influenced by factors like bioavailability and individual responses. Resveratrol's anticancer effects, antidiabetic properties, cardioprotective mechanisms, hepatoprotective benefits, neuroprotective potential, and antimicrobial activities highlight its versatility in addressing multifaceted health challenges. This review examines resveratrol's health benefits through a systematic analysis of 89 articles from 2000 to 2023. Using keywords like "resveratrol," "health benefits," and "chronic diseases" in searches on platforms such as PubMed, Google Scholar, and ScienceDirect, the study focuses on its antiangiogenic, immunomodulatory, antimicrobial, and neuroprotective properties. As ongoing research continues to unravel the full spectrum of resveratrol's capabilities, it remains a subject of interest for potential pharmaceutical applications in combating diverse human diseases.

Despite the quantities and diversity of chemical compounds such as flavonoids discovered in lemongrass (Cymbopogon citratus DC.), available data are fragmentary. Their variation depending on the type of extract and origin of the plant and their effect on biological activities are not deeply discussed. Therefore, this paper provides a critical discussion of bioactive compounds including flavonoid content in extracts of Cymbopogon citratus, and their associated biological properties. Recorded data showed that recent studies have addressed the flavonoids qualitatively and quantitatively in various extracts of C. citratus. Existing literature clarified a significant variation of chemicals depending on the used parts of the plants. However, data on the effects of climate change and other environmental on the quantity and quality of flavonoids are not yet available. On the other hand, the recorded flavonoids were associated with a wide range of pharmacological properties including antioxidant, anti-inflammation, anti-microbial, and anti-diabetic effects, which are variable depending on the types of flavonoids. Other properties such as anticancer, analgesic, and diuretic activities are not yet investigated in the flavonoids extracted from the plant, thus more advanced studies are needed to optimize the extraction of biomolecules counting flavonoids, and then apply them to the most devastating diseases and pathogens.