NOTCH Signaling Pathway: Occurrence, Mechanism, and NOTCH-Directed Therapy for the Management of Cancer.

It is now well understood that many signaling pathways are vital in carrying out and controlling essential pro-survival and pro-growth cellular functions. The NOTCH signaling pathway, a highly conserved evolutionary signaling pathway, has been thoroughly studied since the discovery of NOTCH phenotypes about 100 years ago in Drosophila melanogaster. Abnormal NOTCH signaling has been linked to the pathophysiology of several diseases, notably cancer. In tumorigenesis, NOTCH plays the role of a "double-edged sword," that is, it may act as an oncogene or as a tumor suppressor gene depending on the nature of the context. However, its involvement in several cancers and inhibition of the same provides targeted therapy for the management of cancer. The use of gamma (γ)-secretase inhibitors and monoclonal antibodies for cancer treatment involved NOTCH receptors inhibition, leading to the possibility of a targeted approach for cancer treatment. Likewise, several natural compounds, including curcumin, resveratrol, diallyl sulfide, and genistein, also play a dynamic role in the management of cancer by inhibition of NOTCH receptors. This review outlines the functions and structure of NOTCH receptors and their associated ligands with the mechanism of the signaling pathway. In addition, it also emphasizes the role of NOTCH-targeted nanomedicine in various cancer treatment strategies.

Effective seed cake extract of O. sanctum inducing the p53 dependent apoptotic pathway in oral cancer cells.

OBJECTIVE: Present study was to observe the therapeutic aspects of seed cake extracts of Ocimum sanctum against the oral cancer cell line with the activation of p53 apoptotic pathway. METHOD: Seed cake extracts were characterized using GC-MS analysis. Cytotoxic activity was observed on KB cells and L929 cell through MTT assay and scratch assay. Antioxidant activity on KB cells were determined using enzymatic and non enzyme content in the treated cells. Chick chorioallantoic membrane (CAM) was established to check the presence of blood vessel formation and neuvasculature pattern in the treated fertilized eggs. DNA fragmentation and gene expression studies were also determined in the treated cells to check the upregulation of apoptotic pathways. RESULTS: GC-MS analysis confirmed alkaloids, phenols, and many. The cytotoxic activity showed maximum antiproliferative potential with aqueous extract, whereas no cytotoxic effect was observed on L929 cells. The ethanolic and aqueous extract has shown a greater SI value. Scratch assay has signified that aqueous extract has a lower migration rate of KB cells. Aqueous extract showed maximum enzymatic activity and lower malondialdehyde content in cells treated with ethanolic extract. CAM model confirmed that eggs treated with aqueous extract has shown inhibition of vasculature pattern and dissolutions of blood vessels. DNA Fragmentation and Gene expression studies confirmed maximum fold in the KB cell treated with an aqueous extract of seed cake leading to activation of p53 dependent apoptotic pathway. CONCLUSION: The potent therapeutic properties of seed cake extracts have been proven, and they can be used as herbal treatments to prevent oral cancer.

Novel biogenic silver nanoconjugates of Abrus precatorius seed extracts and their antiproliferative and antiangiogenic efficacies.

Biogenic silver nanoconjugates (AgNCs), derived from medicinal plants, have been widely explored in the field of biomedicines. AgNCs for the first-time were synthesized using ethyl acetate seed extracts of Abrus precatorius and their antiproliferative and antiangiogenic efficacies were evaluated against cervical and oral carcinoma. Ultraviolet-Visible spectrophotometry, dynamic light Scattering (DLS), and scanning electron microscopy (SEM) were used for characterization of AgNCs. Antiproliferative activity was investigated using MTT, DNA fragmentation and in-vitro antioxidant enzyme activity assays. In-vivo chick chorioallantoic membrane (CAM) model was used to evaluate antiangiogenic activity. A total of 11 compounds were identified in both the extracts in GCMS analysis. The synthesized AgNCs were spherical shaped with an average size of 97.4 nm for AgAPE (Sox) and 64.3 nm for AgAPE (Mac). AgNCs possessed effective inhibition against Hep2C and KB cells. In Hep2C cells, AgAPE (Mac) revealed the highest SOD, catalase, GST activity and lower MDA content, whereas AgAPE (Sox) showed the highest GSH content. On the other hand, in KB cells, AgAPE (Sox) exhibited the higher SOD, GST activity, GSH content, and least MDA content, while AgAPE (Mac) displayed the highest levels of catalase activity. Docking analysis revealed maximum binding affinity of safrole and linoleic acid with selected targets. AgAPE (Sox), AgAPE (Mac) treatment profoundly reduced the thickness, branching, and sprouting of blood vessels in the chick embryos. This study indicates that A. precatorius-derived AgNCs have enhanced efficacies against cervical and oral carcinoma as well as against angiogenesis, potentially limiting tumour growth.

Nutritional Assessment of Lactarius drassinus and L. controversus from the Cold Desert Region of the Northwest Himalayas for Their Potential as Food Supplements.

Kargil is a cold desert with hostile ecological conditions such as low temperature and precipitation, as well as difficult terrains. However, several wild mushrooms thrive well under such an extreme environment. Despite their abundance, the chemical composition of indigenous mushrooms has not been explored. This study aimed to assess the potential of two wild edible mushrooms from Kargil, Lactarius drassinus and Lactarius controversus, as food supplements by evaluating their nutritional and nutraceutical properties. Nutritional attributes such as total protein, available carbohydrates, soluble sugars, and vitamins were found to be high in the mushroom species. Furthermore, high mineral accumulation and relatively lower antinutrient concentrations resulted in higher bioavailabilities of Zn, Fe, Ca, and Mg. Gas-chromatography-mass-spectrometry-based metabolite profiling revealed that although the two mushroom species showed similar metabolite compositions, their relative concentrations differed. Sugars were the predominant compounds identified in both the species, with sugar alcohols being the major contributor. The second most abundant class of compound in L. drassinus was amino acids, with 5-oxoproline as the major contributor. On the other hand, fatty acids were the second most abundant compounds in L. controversus, with high oleic and linoleic acid concentrations. In the ultra-performance-liquid-chromatography-based quantification of phenolic compounds, chlorogenic acid was found to be highest in in terms of its concentration in both the mushrooms studied, followed by quercetin dihydrate and gallic acid in L. drassinus and L. controversus, respectively. Moreover, high antioxidant activities attributable to their high phenol, flavonoid, and carotenoid concentrations were observed. Overall, the two mushrooms offer well-balanced sources of nutritional and nutraceutical compounds, making them healthy foods.

A New RP-HPLC Method for Simultaneous Determination of Amaroswerin, Amarogentin and Andrographolide in a Herbal Drug "Chirayata".

Chirayata-the whole dried plant of Swertia chirayita-is an important traditional drug of Indian System of Medicines. A novel reverse-phase high performance liquid chromatography (RP-HPLC) method has been developed for the simultaneous determination and quantification of amaroswerin, amarogentin and andrographolide in a herbal drug "Chirayata," which is oftenly adulterated/substituted with herbal drug Kalmegh. The developed method is in accordance with International Council for Harmonization guidelines and is simple, precise, accurate, rapid, reproducible and specific to determine amarogentin, amaroswerin and andrographolide. Reverse-phase column (Water's X-bridge C18, 5 µm, 4.6 mm × 250 mm) with high resolution for all marker compounds was used with binary gradient elution (methanol:water) with a flow rate of 1 mL/min and detection at 235 nm. The developed method showed good linearity (R2 > 0.999) in a relatively wider range of concentration 2.968-95.00 ppm for amarogentin, amaroswerin and 5.625-180 ppm for andrographolide. The method is important for quality control analysis of drug Chirayata.

Antiproliferative efficacy of the antioxidant bioactive compounds of defatted seeds of Azadirachta indica and Momordica charantia against the regulatory function of tumor suppressor gene inducing oral carcinoma.

The present study focuses on the antiproliferative activity of polyphenolic flavonoids found in defatted seeds of Azadirachta indica and Momordica charantia with the regulatory function of tumor suppressor genes inducing Oral Squamous Cell Carcinoma. Polyphenolic flavonoid in extracts was characterized using chromatographic analysis and has confirmed the presence of quercetin, rutin and tannic acid in the extracts of A. indica and M. charantia. According to DPPH assay and reducing power assays, free radical scavenging was found to be high in ethanolic extract of defatted seeds. Antiproliferative efficacies of defatted seed extracts against KB cell line (mouth) were studied by MTT assay and revealed that aqueous extract of defatted seeds of M. charantia has exhibited maximum antiproliferative activity against KB cells. Antioxidant activity of defatted seed extracts were observed on treated KB cells by determining enzymatic activity (SOD, Cat, and GST) and nonenzyme content (GSH and MDA Content). Using the AutoDock tool, quercetin, rutin and tannin acid revealed that mutant p53, TWIST related protein, TGF-ß and Snail I have the best binging energy results. MD simulation was observed on best docking results between the molecule and identified flavonoid by Desmond V 5.9 package . This leads to the conclusion that bioactive extracts with antiproliferative activity, antioxidant capacity and polyphenols with binding efficacy against tumor suppressor gene regulatory function could be used as a herbal remedy.Communicated by Ramaswamy H. Sarma.

In-vitro antiproliferative efficacy of Abrus precatorius seed extracts on cervical carcinoma.

Abrus precatorius is a tropical medicinal plant with multiple medicinal benefits whose seeds have not yet been studied against cervical cancer. Herein, we have assessed the antioxidant and antiproliferative properties of seed extracts (ethyl acetate and 70% ethanol) prepared from Soxhlet and Maceration extraction methods against Hep2C and HeLa Cells. We observed that the APE (Sox) extract had a significantly higher total flavonoid content, APA (Mac) extract had a high total phenolic content, and APA (Sox) extract had a high total tannin content. Further, HPLC analysis of extracts revealed the presence of tannic acid and rutin. Moreover, APA (Sox) exhibited the highest free radical scavenging activity. APE (Mac) had the best antiproliferative activity against Hep2C cells, while APA (Sox) had the best antiproliferative activity against HeLa cells. In Hep2C cells, APE (Mac) extract revealed the highest SOD, catalase activity, GSH content, and the lowest MDA content, whereas APA (Mac) extract demonstrated the highest GST activity. In HeLa cells, APA (Sox) extract showed the highest SOD, GST activity, GSH content, and the least MDA content, whereas APA (Mac) extract showed the highest catalase activity. Lastly, docking results suggested maximum binding affinity of tannic acid with HER2 and GCR receptors. This study provides evidence that A. precatorius seed extracts possess promising bioactive compounds with probable anticancer and antioxidant properties against cervical cancer for restricting tumor growth.

Ethnomycological study of wild edible and medicinal mushrooms in district Jammu, J&K (UT), India.

BACKGROUND: Union Territory of Jammu and Kashmir (J&K) has a rich tradition of usage of wild edible mushrooms (WEMs) for culinary and medicinal purposes. But very few studies, restricted to some regions of the Union Territory, have been conducted to enlist the WEM. District Jammu has never been explored for WEM. Moreover, the quantification of the traditional knowledge of WEM has not been carried out as yet in J&K. Therefore, the present study was conducted in the Jammu district with the aims of enlisting the WEM and its usage, finding the most used WEM, and enumerating the consensus of usage for a species and associated knowledge. METHODS: A total of 192 informants between the age of 25 and 87 years were interviewed. The collected information was organized and arranged based on use reports for quantitative analysis. The cultural importance index (CI) and factor informant consensus (Fic) were calculated to estimate the cultural importance and to test homogeneity of information and knowledge sharing about WEM, respectively. Analysis of variance was used to evaluate the significance of differences in the usage of WEM among different informant categories. RESULTS: Results of the present study show that the locals were having knowledge of fourteen fleshy fungi that are mainly utilized for culinary purposes. They also stated various medicinal values of some of these fungi. Agaricaceae and Lyophyllaceae were the most used families, and Termitomyces (5 species) was the most represented genus. Based on CI values, Termitomyces sp. (CI 0.57) was the most important and diversely used species. Termitomyces heimii, Termitomyces clypeatus, and Termitomyces striatus var. annulatus were the other culturally important and frequently consumed species by the locals. More than 78.6% of these WEM were new records as culinary and medicinal for J&K (UT). The values of factor informant consensus (Fic) varied between 0.98 (culinary) and 0.76 (skin diseases). Females, elders, and informants who have not attended schools were having significantly (P < 0.05) higher information regarding WEM. CONCLUSION: The inhabitants of district Jammu had good knowledge of WEM, but no documentation, lying of most of the information with elders and uneducated people, and destruction of forests and other natural habitats of WEM pose a serious threat of losing this valuable information in near future. An ardent need is to educate locals regarding regionally available WEM. Further studies are recommended for developing protocols of cultivation of these WEM so that their future availability is ascertained along with creating income resources for the local population.

Preclinical assessment of stem of Nicotiana tabacum on excision wound model.

Agro-waste material derived from N. tabacum has shown enormous potential antioxidant and antimicrobial activity. Hence in the present study, we investigated the wound healing efficacy of ethanolic extract of stem of Nicotiana tabacum on wistar rat model. Ethanolic extract prepared from defatted stem was to check various phytochemicals using spectrophotometric and chromatographic technique. The antioxidant potential was determined by FRAP and Reducing Power assay in extract. Cytotoxicity of extracts was determined using mouse fibroblast L929 cell lines by MTT assay. In vivo angiogenic activity was observed on chick chorioallantoic membrane (CAM) model by observing blood vessels formation and its branching. In vivo wound healing activity was observed on excision wounds in rat model by quantifying percentage of wound contraction, antioxidant activity and histopathology studies. From the present study, polyphenols, tannins and alkaloids were found to be determined in the ethanolic extract by means of spectrophotometric and chromatographic analysis against standards. Antioxidant assay revealed maximum antioxidant potential in ethanolic extract. Cytotoxic effect of extract has not been shown on L929 cell line. From CAM model, extract has shown growth of blood vessels formation at concentration of 480 µg/ml. Topical application of extracts on excision wounds, revealed wound healing activity i.e. 98.7% ± 0.002 on 14th day as well as enzymatic activity (SOD, CAT, GST) and non enzyme content (GSH and Lipid peroxidation) has been found to be high in granulated tissue. Hisopathological studies confirmed the re-epithelization in skin wounds. It can be concluded that stem of N. tabacum can be used as herbal remedy in wound healing process as a topical application.

Traditionally used wild edible plants of district Udhampur, J&K, India.

BACKGROUND: Wild edible plants (WEPs) refer to edible species that are not cultivated or domesticated. WEPs have an important role to play in poverty eradication, security of food availability, diversification of agriculture, generation of income resources, and alleviating malnutrition. In the present study, an inventory of traditionally used WEPs from Udhampur district of J&K, India, has been prepared. METHODS: A systematic and extensive ethnobotanical survey was carried out in different villages of the district for the collection of information on WEPs. The data collected through questionnaire and interviews was then analyzed for cultural importance index (CI) and factor informant consensus (Fic) to know the cultural significance of WEPs and consensus for the knowledge of WEPs among the informants. RESULTS: A total of 90 plant species belonging to 45 families and 78 genera were edible and serve as wild phytofoods in the present study. Species richness of wild edible species was the maximum for vegetables (46 species) followed by fruits (37 species) and medicinal plants (36 species). Culturally (on the basis of CI), the most important vegetable and fruit species were Diplazium esculentum, Fumaria indica, Taraxacum campylodes, Urtica dioica, Phyllanthus emblica, Punica granatum, Cordia dichotoma, Syzygium cumini, Ficus palmata, etc. The highest use-report (626) was recorded for vegetables whereas the maximum mean use-report (14.8) was recorded for fruits. On an average, 20.7 wild edible species were used per informant. Informant consensus index (Fic) varied between 0.83 and 0.94 for raw vegetables and preserved vegetables, respectively. CONCLUSION: One of the most important issues of this era is hunger for which one of the possible solutions is the usage of WEPs. The local populace of Udhampur has good knowledge of WEPs, and this legacy of traditional culture must be conserved.

Ethnomedicinal plants of Shankaracharya Hill, Srinagar, J&K, India.

ETHNOPHARMACOLOGICAL RELEVANCE: Primitive human societies have always relied on plants and plant products for various remedies. In certain areas, these folk medical prescriptions are endemic and have survived through ages from one generation to the next through word of mouth. They do not exist as written knowledge. The present study was undertaken with an objective of documenting the ethnobotanical information of medicinal plants of Shankaracharya Hill by taking the help of local herbalists, elderly and knowledgeable people. MATERIAL AND METHODS: The data was quantitatively analysed using use-value (UV), informant consensus factor (ICF) and fidelity level (Fl%) indices. RESULTS: Total 130 plant species from 57 families and 111 genera were ethno-medicinally utilized by the 103 informants interviewed in the present study. The most used families were Asteraceae, Rosaceae, Lamiaceae, Fabaceae and Brassicaceae. The medicinal plants were mainly herbs (79.2%). Leaves were the most used (27.6%) plant part followed by whole plant (14.8%), root (11.4%) and seed (10.5%). The most important species on the basis of UV were Viola odorata, Taraxacum campylodes, Aesculus hippocastanum, Artemisia absinthium, Daucus carota, Thymus serphyllum, Ephedra gerardiana and Salvia moorcroftiana. The values ICF ranged between 0.93 and 0.76. Only Epilobium hirsutum recorded 100% Fl. Some of the most important medicinal plants with high Fl values were Tribulus terrestris, Asparagus officinalis, Trifolium repens, Anemone biflora, Melia azedarach, A. absinthium, Lonicera quinquelocularis, Rosa webbiana, D. carota, Oxalis corniculata and Potentilla reptans. CONCLUSION: The contribution of plant parts collected through destructive methods was 29.5%. Harvesting of roots, rhizomes, bulbs and corm kills the parent plant and could be a severe threat for survival of the often rare and slowly reproducing medicinal plants, and therefore need sustainable utilization and conservation strategies. Ethnomedicinal species like A. absinthium, A. hippocastanum, D. carota, M. azedarach, T. campylodes, T. serphyllum, T. terrestris having high number of citations, UV and FL should be analyzed for phytochemicals and pharmacology.

Traditional phytoremedies for the treatment of menstrual disorders in district Udhampur, J&K, India.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbal remedies form an integral part of healing and are considered to be the oldest forms of health care known to mankind. The present study aims to document traditional phytoremedies for the treatment of menstrual disorders in Udhampur district of J&K, India. MATERIAL AND METHODS: The informants were interviewed directly and information was gathered about plants used in different menstrual disorders. The data was further analyzed for use-value (UV), factor informant consensus (Fic) and fidelity level (Fl). RESULTS: In all, 62 informants were interviewed. Most of the informants (66%) were females. The patients prefer female healers over male vaids and hakims. A total of 50 plants were used to cure different menstrual disorders. Seeds were found to be of utmost medicinal importance (43.8%) followed by leaves (20.8%) and fruits (16.7%). Oral administration was observed to be the main mode (90.0%) of intake of medicine. The plants with high use-value were Triticum aestivum (UV=1.76), Taraxacum officinale (UV=1.16), Citrus limon (UV=0.95), Allium cepa (UV=0.79), Cicer arietinum (UV=0.77), Trigonella foenum-graecum (UV=0.66), Rubia manjith (UV=0.56), Ocimum tenuiflorum (UV=0.56) and Oryza sativa (UV=0.52). The various menstrual disorders were classified into 7 categories. The values of Fic varied between 0.96 (dysmenorrhea, itching and foul smell) and 0.92 (menorrhagia). The 100% Fl value was scored by 20 plants. Leucorrhea reported the highest 5 plants with 100% Fl. Nearly 40% of the formulations had two or more plants. CONCLUSION: Plants used for the treatment of different menstrual disorders were documented and analyzed for ethnogynecological problems. The study revealed some plants like Triticum aestivum, Rubia manjith, Dalbergia sissoo, Raphanus sativus, Citrus limon, Allium cepa, Trigonella foenum-graecum, Elettaria cardamomum etc. to be of great importance vis a vis menstrual disorders. Further pharmacological studies of these plants may provide some important drugs for the treatment of common menstrual disorders.

Ethnomedicinal plants used to treat skin diseases by Tharu community of district Udham Singh Nagar, Uttarakhand, India.

ETHNOPHARMACOLOGICAL RELEVANCE: Tharu community is the largest primitive indigenous community of the Uttarakhand, India. In this article we have scientifically enumerated medicinal plants and herbal preparations used by the Tharu community to treat various skin diseases, and discussed dermatological properties of these plants in the light of previous ethnomedicinal, microbiological, pharmacological, toxicological, phytochemical and clinical studies. MATERIALS AND METHODS: Ethnomedicinal survey was conducted in different villages of Tharu community located in district Udham Singh Nagar, Uttarakhand, India. Ethnomedicinal information on plants used to treat various skin diseases was collected from 122 individuals (93 males and 29 females), including 35 experienced herbal practitioners and 87 local villagers. For each of the recorded plant species the use value (UV) and fidelity level (FL) was calculated. The informant consensus factor (Fic) was also calculated to find out the homogeneity in the information given by the informants. RESULTS: A total of 90 plant species belonging to 86 genera and 48 families were used by the Tharu community to treat various skin diseases viz., wounds (38 spp.), boils (32 spp.), cuts (18 spp.), leprosy (11 spp.), eczema (10 spp.), itching (7 spp.), ringworm (5 spp.), burns (4 spp.), leucoderma (4 spp.), cracked heels (2 spp.), dandruff (3 spp.), body infection (2 spp.), chilblains (2 spp.), hair fall (2 spp.) and toes infection (2 spp.). Information on botanical name, family, vernacular name, ailments treated, mode and dose of herbal preparations, UV and FL values are provided for each of the recorded species. According to UV value most preferred plant species used to treat skin diseases by Tharu community was Ricinus communis L. followed by Tridax procumbens (L.) L., Azadirachta indica A. Juss., Ageratum conyzoides and Allium cepa L. CONCLUSIONS: The present study has revealed significant information on various medicinal plants used to treat skin diseases by Tharu community. Literature review has confirmed most of the claims made by the Tharu community regarding treatment of various skin diseases by the reported plants. The literature review has also revealed that products from very few of the reported plants are available in market, while most of the reported plants are still under preclinical or clinical trials. There are various known phytochemicals, and antibiotic, antibacterial, antiviral and antifungal agents present in these plants which may be synthesized or transformed to make pharmaceuticals. Some of the reported plants have shown promising results in preclinical trails and there is a need of clinical trials to see their safety and efficacy in treating various skin diseases. These plants may be targeted for development of new medicines, ointments or drugs for the treatment of skin diseases. However further toxicological, preclinical and clinical studies are needed to validate claims about little worked out plant species reported in the present study viz., Sida cordata (Burm. F.) Borss. Waalk., Millettia extensa (Benth.) Baker, Caesulia axillaris Roxb., Ehretia laevis Roxb., Vanda tessellate (Roxb.) Hook. Ex G.Don. and Eualaliopsis binata (Retz.) C.E. Hubb. Further studies on these plants are recommended to assess their potential in development of new skin care products.

Ethnomedicinal plants used by the villagers of district Udhampur, J&K, India.

UNLABELLED: Plants are an integral part of life in many indigenous communities. Besides, being the source of food, fodder, fuel, etc., the use of plants as herbal medicines in curing several ailments goes parallel to the human civilization. Ethnopharmacology involves the investigation of the plants used by the traditional communities and further understand the pharmacological basis of these culturally important medicinal plants. Present study was conducted to enlist the medicinal plants used by the local inhabitants of Udhampur district of Jammu and Kashmir, India. MATERIAL AND METHODS: Direct interviews of the 182 informants were conducted. The data generated through interviews was analysed using quantitative tools like use-value, factor informant consensus and fidelity level. RESULTS: A total of 166 species of flowering plants belonging to 63 families and 145 genera were observed to be medicinal and used to cure 78 ailments. Medicinal plants were mainly from Asteraceae, Solanaceae, Lamiaceae, Poaceae, Fabaceae and Amaranthaceae families. Leaves were the most used plant part in the medicinal preparations. The most important medicinal species of the present study site as per the use-value (UV) were: Achyranthes aspera, Zanthoxylum armatum, Acorus calamus, Syzygium cumini, Phyllanthus emblica, Plumbago zeylanica etc. The important ailment categories classified on the basis of factor informant consensus (Fic) were diabetes, external parasite, liver complaints and gastrointestinal disorders. The maximum number of species was utilized to cure gastrointestinal and dermatological ailments. Important species for each ailment category were also assessed using fidelity level. It was found that the older informants provided more information about the ethnomedicinal plants, but this valuable treasure of traditional knowledge is depleting significantly with the decrease in age and increase in educational level. CONCLUSION: The results of present ethnobotanical survey reveal the rich wealth of indigenous knowledge associated with the villagers of Udhampur district. A number of plants with a high citation values have given some leads for the further pharmocological research. Apart from these highly cited plants, studies need to be done on some other promising plants like Anagallis arvensis, Euphorbia hirta, Ficus benghalensis, Fumaria indica, Prunus persica, Rubus ellipticus, Taraxacum officinale, Tribulus terrestris etc.