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.

Comparative assessment of morphological, physiological and phytochemical attributes of cultivated Valeriana jatamansi Jones in Uttarakhand, West Himalaya.

Medicinal plants are global sources of herbal products, drugs, and cosmetics. They are disappearing rapidly due to anthropogenic pressure, overexploitation, unsustainable harvesting, lack of knowledge on cultivation, and the availability of quality plating materials. In this context, standardized in-vitro propagation protocol was followed to produce Valeriana jatamansi Jones, and transferred in two locations at Kosi-Katarmal (GBP) Almora (1200 masl) and Sri Narayan Ashram (SNA) Pithoragarh (Altitude 2750 masl), Uttarakhand. Over the three years of growth, plants were gathered from both locations for determining biochemical and physiological parameters, and growth performance. The plants growing at Sri Narayan Ashram (SNA) showed considerably (p < 0.05) higher amounts of polyphenolics, antioxidant activities, and phenolic compounds. Similarly, physiological parameters (transpiration 0.004 mol m-2 s-1; photosynthesis 8.20 µmol m-2 s-1; stomatal conductance 0.24 mol m-2 s-1), plant growth performance (leaves number 40, roots number 30, root length 14 cm) and soil attributes (total nitrogen 9.30; potassium 0.025; phosphorus 0.34 mg/g, respectively) were found best in the SNA as compared to GBP. In addition, moderate polar solvent (i.e., acetonitrile and methanol) was found suitable for extracting higher bioactive constituents from plants. The findings from this study revealed that large-scale cultivation of V. jatamansi should promote at higher elevation areas such as Sri Narayan Ashram to harness the maximum potential of the species. Such a protective approach with the right interventions will be helpful to provide livelihood security to the local populace along with quality material for commercial cultivation. This can fulfill the demand through regular supply of raw material to the industries and simultaneously promote their conservation.

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.

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.

Anti-oxidant and anti-microbial properties of some ethno-therapeutically important medicinal plants of Indian Himalayan Region.

Therapeutic potential of medicinal plants as a source of noble natural anti-oxidants and anti-microbial agents has been well recognised all across the globe. In this study, phenolic compounds, in vitro anti-oxidant activity and anti-microbial properties have been investigated in five Himalayan medicinal plants, (e.g., Acorus calamus, Habenaria intermedia, Hedychium spicatum, Roscoea procera and Valeriana jatamansi) in different solvent systems. R. procera exhibited significantly (p < 0.05) higher phenolics; while H. spicatum was rich in flavonoids and V. jatamansi in anti-oxidant activity. Also, R. procera and H. spicatum were found rich in gallic acid; V. jatamansi in catechin, hydroxylbenzoic acid and caffeic acid and H. intermedia in hydroxyl benzoic acid. Solvent systems showed species specific response for extraction of total flavonoids and anti-oxidant activity. All the extracts were found effective against different bacterial and fungal strains in a dose dependent manner and maximum antimicrobial activity was found in R. procera as compared to other species. All the plant extracts showed greater activity against bacterial strains as compared to fungal strains. The results of this study suggest that extract of these species can be used as natural anti-oxidant to reduce free radical mediated disorders and as natural alternative for food preservation.

Effect of Processing and Storage Methods on the Nutritional, Anti-nutritional, and Anti-oxidant Properties of Paeonia emodi, Wall. ex. Royle.

Nutritional, anti-nutritional, and anti-mutagenic activities of the fresh and boiled Paeonia emodi leaves were analyzed. Significantly higher vitamin A (64.19 ± 0.18 mg/100 g), C (160.50 ± 1.85 mg/100 g), and E (1.25 ± 0.00 µg/g) contents were recorded in boiled as compared to fresh and dried juvenile leaves. Similarly, significantly higher protein content (329.63 ± 0.33 mg/100 g) was found in boiled budding leaves, carbohydrate content in fresh juvenile (0.353 ± 0.02) and mature leaves (0.353±0.10 mg/g) , methionine content (47.75 ± 0.09 mg/g) in dried budding stage leaves, and proline content (1.23 ± 0.12 µM/g) in dried mature leaves. Anti-nutritional attributes like phytic acid (250.17 ± 0.19 mg/100 g; p < 0.05) and total tannins (48.41 ± 0.09 mg/g) were significantly higher in dried and fresh budding leaves, respectively; however, trypsin inhibition activity (91.90 ± 0.34 %) was observed in dried juvenile leaves. Significantly higher 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity (71.13 ± 0.09 mM AAE/100 g) and ferric-reducing antioxidant power (FRAP) activity (3.39 ± 0.01 mM AAE/100 g) were recorded higher in dried budding leaves. On the other hand, 2,2-diphenyl-1-picryylhydrazyl (DPPH) free radical scavenging assay (3.55 ± 0.017 mM AAE/100 g) and OH ions (1.69 ± 0.01 mM AAE/100 g) were significantly higher in boiled juvenile leaves and dried mature leaves, respectively. Anti-mutagenic activity of P. emodi extract revealed varying levels of protection against DNA damaging agents. The aqueous extract of P. emodi at budding leaves (500 µg dried) showed comparatively better protective activity as compared to other growth stages. Results of this investigation indicated that the species have nutritional and medicinal value and therefore can be a potential source for nutraceutical and pharmaceutical industries.

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.