Anticancer potential of alkaloids: a key emphasis to colchicine, vinblastine, vincristine, vindesine, vinorelbine and vincamine.

Cancer, one of the leading illnesses, accounts for about 10 million deaths worldwide. The treatment of cancer includes surgery, chemotherapy, radiation therapy, and drug therapy, along with others, which not only put a tremendous economic effect on patients but also develop drug resistance in patients with time. A significant number of cancer cases can be prevented/treated by implementing evidence-based preventive strategies. Plant-based drugs have evolved as promising preventive chemo options both in developing and developed nations. The secondary plant metabolites such as alkaloids have proven efficacy and acceptability for cancer treatment. Apropos, this review deals with a spectrum of promising alkaloids such as colchicine, vinblastine, vincristine, vindesine, vinorelbine, and vincamine within different domains of comprehensive information on these molecules such as their medical applications (contemporary/traditional), mechanism of antitumor action, and potential scale-up biotechnological studies on an in-vitro scale. The comprehensive information provided in the review will be a valuable resource to develop an effective, affordable, and cost effective cancer management program using these alkaloids.

Sesquiterpenoid lactones as potential anti-cancer agents: an update on molecular mechanisms and recent studies.

Plants-based natural compounds are well-identified and recognized chemoprotective agents that can be used for primary and secondary cancer prevention, as they have proven efficacy and fewer side effects. In today's scenario, when cancer cases rapidly increase in developed and developing countries, the anti-cancerous plant-based compounds become highly imperative. Among others, the Asteraceae (Compositae) family's plants are rich in sesquiterpenoid lactones, a subclass of terpenoids with wide structural diversity, and offer unique anti-cancerous effects. These plants are utilized in folk medicine against numerous diseases worldwide. However, these plants are now a part of the modern medical system, with their sesquiterpenoid lactones researched extensively to find more effective and efficient cancer drug regimens. Given the evolving importance of sesquiterpenoid lactones for cancer research, this review comprehensively covers different domains in a spectrum of sesquiterpenoid lactones viz (i) Guaianolides (ii) Pseudoguaianolide (iii) Eudesmanolide (iv) Melampodinin A and (v) Germacrene, from important plants such as Cynara scolymus (globe artichoke), Arnica montana (wolf weeds), Spilanthes acmella, Taraxacum officinale, Melampodium, Solidago spp. The review, therefore, envisages being a helpful resource for the growth of plant-based anti-cancerous drug development.

Diversity of bioactive compounds and antioxidant activity in Delicious group of apple in Western Himalaya.

Apple contributes significantly to the livelihood and health of the people living in Himalayan regions. Among others, the Delicious group of apple is known for their health promoting and income generating attributes. However, the systematic investigation on morphological and phytochemical attributes of the apple growing in Indian Himalayan region is poorly known. An altitude-dependent variation in the fruit quality traits and phytochemical diversity was observed. The Royal Delicious was found rich in total tannin, flavonoids, flavonols, antioxidant activity [2,2-azinobis (3-ethylbenzothiazoline-6-sulphonic acid), 2,2-Diphenyl-1-picryhydrazyl, Ferric reducing antioxidant power], procyanidin B2, phloridzin and gallic acid; Red Delicious for total phenol and epicatechin and Golden Delicious for chlorogenic acid. The cultivar and altitude-dependent variation of phenolic profile in peel and pulp portion emphasizes genotype-specific biosynthesis of phenolic compounds in regulatory mechanisms. It is suggested that selection of suitable altitude and cultivars is required for harnessing the maximum phytochemical and antioxidant activity for benefits to human consumption.

Current Evidence on Molecular Mechanisms of Andrographolide in Cancer.

Cancer, a diverse group of diseases characterized by abnormal cell growth and the potential to spread throughout the body, accounts for approximately 10 million deaths globally each year. Current cancer therapies, including chemotherapy, radiation, and various pharmacological treatments, present several challenges and potential side effects. It is important to differentiate these conventional methods, which often involve synthetic drugs, from adjuvant therapies that might be used in conjunction. As a result, there is an increasing interest in alternative therapies, particularly in agents derived from natural sources for cancer treatment. Secondary metabolites have shown promise in promoting the development of new clinical drugs with various anti-cancer mechanisms. This review focuses on the anti-cancer potential of the novel metabolite Andrographolide, extracted mainly from Andrographis paniculata. The chemopreventive properties and the ability to inhibit various signaling pathways across different types of cancers without side effects posit Andrographolide as a promising natural antitumour agent. The review identified that Andrographolide inhibits multiple signaling pathways, contributing to its anti-proliferative, anti-metastatic, and apoptotic effects in various cancers. The compound's natural origin and lack of adverse side effects make it particularly attractive as a therapeutic agent. However, further detailed studies are needed to fully understand its specific mechanisms and potential clinical applications. Andrographolide presents a compelling option as a natural anticancer agent with the potential to overcome some limitations of traditional cancer treatments. Its broad spectrum of anti-cancer activities and absence of side effects highlight its therapeutic potential. The review highlights that continued research and clinical studies are important for confirming the effectiveness and safety of Andrographolide in human use, alongside optimizing dosage and delivery techniques.

Paclitaxel and its semi-synthetic derivatives: comprehensive insights into chemical structure, mechanisms of action, and anticancer properties.

Cancer is a disease that can cause abnormal cell growth and can spread throughout the body. It is among the most significant causes of death worldwide, resulting in approx. 10 million deaths annually. Many synthetic anticancer drugs are available, but they often come with side effects and can interact negatively with other medications. Additionally, many chemotherapy drugs used for cancer treatment can develop resistance and harm normal cells, leading to dose-limiting side effects. As a result, finding effective cancer treatments and developing new drugs remains a significant challenge. However, plants are a potent source of natural products with the potential for cancer treatment. These biologically active compounds may be the basis for enhanced or less toxic derivatives. Herbal medicines/phytomedicines, or plant-based drugs, are becoming more popular in treating complicated diseases like cancer due to their effectiveness and are a particularly attractive option due to their affordability, availability, and lack of serious side effects. They have broad applicability and therapeutic efficacy, which has spurred scientific research into their potential as anticancer agents. This review focuses on Paclitaxel (PTX), a plant-based drug derived from Taxus sp., and its ability to treat specific tumors. PTX and its derivatives are effective against various cancer cell lines. Researchers can use this detailed information to develop effective and affordable treatments for cancer.

Gut Microbiota Targeted Approach by Natural Products in Diabetes Management: An Overview.

PURPOSE OF REVIEW: This review delves into the complex interplay between obesity-induced gut microbiota dysbiosis and the progression of type 2 diabetes mellitus (T2DM), highlighting the potential of natural products in mitigating these effects. By integrating recent epidemiological data, we aim to provide a nuanced understanding of how obesity exacerbates T2DM through gut flora alterations. RECENT FINDINGS: Advances in research have underscored the significance of bioactive ingredients in natural foods, capable of restoring gut microbiota balance, thus offering a promising approach to manage diabetes in the context of obesity. These findings build upon the traditional use of medicinal plants in diabetes treatment, suggesting a deeper exploration of their mechanisms of action. This comprehensive manuscript underscores the critical role of targeting gut microbiota dysbiosis in obesity-related T2DM management and by bridging traditional knowledge with current scientific evidence; we highlighted the need for continued research into natural products as a complementary strategy for comprehensive diabetes care.

Anti-cancer properties of boswellic acids: mechanism of action as anti-cancerous agent.

With the advent of highly effective plant-based medications with few or no side effects, the use of phytomedicines against complex diseases such as cancer is becoming more widespread. The broadly recognized pentacyclic triterpenes known as boswellic acids (BAs) are derived from the oleogum resin, or frankincense, extracted from the plant species of the genus Boswellia. The frankincense mixture contains various BA types, each having a different potential and helping treat certain cancers. This review focuses on details regarding the traits of the BAs, their roles as anti-cancer agents, the mechanism underlying their activities, and the function of their semi-synthetic derivatives in managing and treating certain cancers. The review also explores the biological sources of BAs, how they are conserved, and how biotechnology might help preserve and improve in vitro BA production. The review concludes that the BAs and their semi-synthetic derivatives are effective against a broad spectrum of cancer cell lines. The detailed information in the review can be helpful for researchers to gain more information about BAs and BA-based medications for efficient and cost-effective cancer treatments.

Recent updates on anticancer mechanisms of polyphenols.

In today's scenario, when cancer cases are increasing rapidly, anticancer herbal compounds become imperative. Studies on the molecular mechanisms of action of polyphenols published in specialized databases such as Web of Science, Pubmed/Medline, Google Scholar, and Science Direct were used as sources of information for this review. Natural polyphenols provide established efficacy against chemically induced tumor growth with fewer side effects. They can sensitize cells to various therapies and increase the effectiveness of biotherapy. Further pharmacological translational research and clinical trials are needed to evaluate theirs in vivo efficacy, possible side effects and toxicity. Polyphenols can be used to design a potential treatment in conjunction with existing cancer drug regimens such as chemotherapy and radiotherapy.

Therapeutic Potential of Neoechinulins and Their Derivatives: An Overview of the Molecular Mechanisms Behind Pharmacological Activities.

Neoechinulins are diketopiperazine type indole alkaloids that demonstrate radical scavenging, anti-inflammatory, antiviral, anti-neurodegenerative, neurotrophic factor-like, anticancer, pro-apoptotic, and anti-apoptotic properties. An array of neoechinulins such as neoechinulins A-E, isoechinulins A-C, cryptoechunilin have been isolated from various fungal sources like Aspergillus sp., Xylaria euglossa, Eurotium cristatum, Microsporum sp., etc. Besides, neoechinulin derivatives or stereoisomers were also obtained from diverse non-fungal sources viz. Tinospora sagittata, Opuntia dillenii, Cyrtomium fortunei, Cannabis sativa, and so on. The main purpose of this review is to provide update information on neoechinulins and their analogues about the molecular mechanisms of the pharmacological action and possible future research. The recent data from this review can be used to create a basis for the discovery of new neoechinulin-based drugs and their analogues in the near future. The online databases PubMed, Science and Google scholar were researched for the selection and collection of data from the available literature on neoechinulins, their natural sources and their pharmacological properties. The published books on this topic were also analysed. In vitro and in vivo assays have established the potential of neoechinulin A as a promising anticancer and anti-neuroinflammatory lead molecule. Neoechinulin B was also identified as a potential antiviral drug against hepatitis C virus. Toxicological and clinical trials are needed in the future to improve the phyto-pharmacological profile of neoquinolines. From the analysis of the literature, we found that neoechinulins and their derivatives have special biological potential. Although some modern pharmacological analyzes have highlighted the molecular mechanisms of action and some signalling pathways, the correlation between these phytoconstituents and pharmacological activities must be validated in the future by preclinical toxicological and clinical studies.

Genome-wide transcriptional analysis unveils the molecular basis of organ-specific expression of isosteroidal alkaloids biosynthesis in critically endangered Fritillaria roylei Hook.

Fritillaria roylei Hook. is a critically endangered high altitude Himalayan medicinal plant species with rich source of pharmaceutically active structurally diverse steroidal alkaloids. Nevertheless, except few marker compounds, the chemistry of the plant remains unexplored. Therefore, in the current study, transcriptome sequencing efforts were made to elucidate isosteroidal alkaloids biosynthesis by creating first organ-specific genomic resource using bulb, stem, and leaf tissues derived from natural populations of Indian Himalayan region. Overall, 349.9 million high quality paired-end reads obtained using NovaSeq 6000 platform were assembled (de novo) into 82,848 unigenes and 31,061 isoforms. Functional annotation and organ specific differential expression (DE) analysis identified 2488 significant DE transcripts, grouped into three potential sub-clusters (sub-cluster I: 728 transcripts; sub-cluster II: 446 transcripts and Sub-cluster III: 1314 transcripts). Subsequently, pathway enrichment (GO, KEGG) and protein-protein network analysis revealed significantly higher enrichment of phenyl-propanoid and steroid backbone including terpenoid, sesquiterpenoid and triterpenoid biosynthesis in bulb. Additionally, upregulated expression of cytochrome P450, UDP-dependent Glucuronosyltransferase families and key transcription factor families (FAR1, bHLH, GRAS, C2H2, TCP and MYB) suggests 'bulb' as a primary site of MVA mediated isosteroidal alkaloids biosynthesis. The comprehensive elucidation of molecular insights in this study is a first step towards the understanding of isosteroidal alkaloid biosynthesis pathway in F. roylei. Furthermore, key genes and regulators identified here can facilitate metabolic engineering of potential bioactive compounds at industrial scale.

Ginkgo biloba flavonoid glycosides in antimicrobial perspective with reference to extraction method.

The present study aims to investigate the effect of extraction method on the recovery of flavonoid glycosides, antimicrobials and antioxidants from Ginkgo leaves collected from six different locations in Uttarakhand, Indian Himalaya. Four extraction methods, namely maceration, reflux, shaker and soxhlet were considered, where reflux extracts showed higher antimicrobial antioxidant activity and higher content of flavonoid glycosides. The reference standards of Ginkgo flavonoid glycosides (quercetin, kaempferol and isorhamnetin) and crude extracts were tested for their antimicrobial activity against gram positive and gram negative bacteria and fungi following disc diffusion method and minimum inhibitory concentration (MIC). All the test microorganisms were observed to be inhibited significantly by Ginkgo flavonoids in plate based assays. Correlation coefficients exhibited the extent of contribution of flavonoid glycosides in antimicrobial activity and confirmed the reflux method as a potential method for extraction. Moreover, antioxidant activity as measured by DPPH assay was also found to be higher in reflux method. Significant variation (p < 0.05) in the flavonoid glycosides among the locations was also observed and sample collected from GB6 location was found to be the best for quercetin and isorhamnetin, while GB5 for kaempferol. Significant correlation (r < 0.05, r < 0.001) was obtained while developing the relationship between total flavonoid glycosides and antimicrobials. The present study, thus suggests the reflux method of extraction to be the best for maximum recovery of flavonoid glycosides with higher antioxidant and antimicrobial activities from Ginkgo extract.

Population Genetic Structure and Marker Trait Associations Using Morphological, Phytochemical and Molecular Parameters in Habenaria edgeworthii-a Threatened Medicinal Orchid of West Himalaya, India.

Habenaria edgeworthii Hook. f. ex Collett is an important terrestrial orchid used in different Ayurvedic formulations. In the present study, variations among morphological, phytochemical and molecular markers were assessed. A significant difference was observed among populations using morphological traits. Inter-simple sequence repeat (ISSR) data revealed lower genetic diversity at population level (He = 0.207) as compared to species level (He = 0.334). Analysis of molecular variance (AMOVA) indicates 74 % variation among populations and 26 % within population. Tuber extracts showed significantly (p < 0.05) higher total phenolics and flavonoids among the populations. Antioxidant activity determined by 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and ferric reducing antioxidant power (FRAP) assays exhibited considerable antioxidant potential. Furthermore, the associations between molecular and morphological and phytochemical attributes were studied using multiple regression analysis (MRA). Several ISSR fragments were associated with some morphological and phytochemical traits. These ISSR fragments can be useful for breeding programme of the species when no other genetic information, such as linkage maps and quantitative trait loci, is available.

Chemical composition and antibacterial activity of essential oil of Nepeta graciliflora Benth. (Lamiaceae).

The chemical composition of the essential oil obtained from aerial parts of Nepeta graciliflora was analysed, for the first time, by GC-FID and GC-MS. A total of 27 compounds were identified, constituting over 91.44% of oil composition. The oil was strongly characterised by sesquiterpenes (86.72%), with ß-sesquiphellandrene (28.75%), caryophyllene oxide (12.15%), α-bisabolol (8.97%), α-bergamotene (8.51%), ß-bisabolene (6.33%) and ß-Caryophyllene (5.34%) as the main constituents. The in vitro activity of the essential oil was determined against four micro-organisms in comparison with chloramphenicol by the agar well diffusion and broth dilution method. The oil exhibited good activity against all tested organisms.

Optimization extraction conditions for improving phenolic content and antioxidant activity in Berberis asiatica fruits using response surface methodology (RSM).

This study for the first time designed to optimize the extraction of phenolic compounds and antioxidant potential of Berberis asiatica fruits using response surface methodology (RSM). Solvent selection was done based on the preliminary experiments and a five-factors-three-level, Central Composite Design (CCD). Extraction temperature (X1), sample to solvent ratio (X3) and solvent concentration (X5) significantly affect response variables. The quadratic model well fitted for all the responses. Under optimal extraction conditions, the dried fruit sample mixed with 80% methanol having 3.0 pH in a ratio of 1:50 and the mixture was heated at 80 °C for 30 min; the measured parameters was found in accordance with the predicted values. High Performance Liquid Chromatography (HPLC) analysis at optimized condition reveals 6 phenolic compounds. The results suggest that optimization of the extraction conditions is critical for accurate quantification of phenolics and antioxidants in Berberis asiatica fruits, which may further be utilized for industrial extraction procedure.

Impact of Altitudes and Habitats on Valerenic Acid, Total Phenolics, Flavonoids, Tannins, and Antioxidant Activity of Valeriana jatamansi.

The changes in total phenolics, flavonoids, tannins, valerenic acid, and antioxidant activity were assessed in 25 populations of Valeriana jatamansi sampled from 1200 to 2775 m asl and four habitat types of Uttarakhand, West Himalaya. Significant (p < 0.05) variations in total phenolics, flavonoids, valerenic acid, and antioxidant activity in aerial and root portions and across the populations were observed. Antioxidant activity measured by three in vitro antioxidant assays, i.e., 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic) (ABTS) radical scavenging, 2,2'-diphenyl-1-picryylhydrazyl (DPPH) free radical scavenging, and ferric-reducing antioxidant power (FRAP) assays, showed significant (p < 0.05) differences across the populations. However, no clear pattern was found in phytochemicals across the altitudinal range. Among habitat types, (pine, oak, mixed forest, and grassy land), variation in phytochemical content and antioxidant activity were observed. Equal class ranking, neighbor-joining cluster analysis, and principal component analysis (PCA) identified Talwari, Jaberkhet, Manjkhali, and Khirshu populations as promising sources with higher phytochemicals and antioxidant activity. The results recommended that the identified populations with higher value of phytochemicals and antioxidants can be utilized for mass multiplication and breeding program to meet the domestic as well as commercial demand.