Nutritional Herbs Research Articles

Pharmacological Activities, Phytochemistry and Traditional Uses of Moringa oleifera

Moringa oleifera Lam., more commonly referred to as munga, is a plant that is widely cultivated in India and is used for medicinal purposes. In the family Moringaceae, it is classified as a member. The fact that this plant possesses a multitude of advantageous pharmacological effects, including as anti-diabetic, hepatoprotective, anti-inflammatory, anti-fertility, anti-cancer, anti-microbial, and antioxidant qualities, makes it an appealing nutritional herb. Different names for this species include the horse radish tree and the drumstick tree, to mention only two of them. Each and every part of this plant contains a component that can be utilised for medical purposes. Milk protein, vitamin A, and vitamin C are all found in high concentrations in this food. There are many different chemicals that are considered to be active phytoconstituents. These substances include proteins, quinine, saponins, flavonoids, tannin, steroids, glycosides, fixed oils, and lipids. This plant also has a home in the tropical regions of the world. These are some extra components that are included: both niazinin A and niazinin B, as well as niazimicin A and niaziminin B. In the fight against malnutrition, the plant's high phytonutrient concentration makes it an effective natural integrator that complements other natural remedies. The findings of studies that investigated the phytochemistry of different plant parts have shown that plants contain a large quantity of organic molecules, which include both primary and secondary metabolites. After doing research on the pharmacological and nutraceutical properties of the plant, it has been determined that it can be utilised in the treatment of a variety of ailments. Through this review, the phytochemical composition of the plant, as well as its therapeutic applications and pharmacological effects, are discussed in depth.

Abstract PO1-08-09: Drynaria fortunie, a nutritional herb for prevention in triple negative breast cancer

Abstract Study Rationale: The triple negative breast cancer (TNBC) lacks the expression of hormone and growth factor receptors and responds only to anthracycline/taxol-based conventional chemotherapy. Major therapeutic limitations include systemic toxicity and acquired resistance to chemo-therapeutics. Relatively non-toxic nutritional herbs from traditional Chinese medicine (TCM) may represent testable alternatives against TNBC. These herbs effectively target multiple signaling pathways (Yang et al: J. Ethno-pharmacology 264: 113249, 2021). Growth inhibitory efficacy of nutritional herbs in a cellular model for TNBC is associated with downregulation of RB, RAS, PI3K and AKT signaling pathways (Telang et al: Pharmaceuticals 14: 1318, 2021). Drynaria fortunie (DF) is a nutritional herb that is used in many TCM herbal formulations. The present study is designed to examine the effects of DF in a cellular model for TNBC and to identify mechanistic leads for its efficacy. Experimental Model, herbal extract and biomarkers: Estrogen receptor negative, progesterone receptor negative and human epidermal growth factor receptor-2 negative MDA-MB-231 human breast cancer cell line represented a cellular model for TNBC. Non-fractionated aqueous extract from the bark of DF represented the test agent. Cell cycle progression, RB signaling and caspase 3/7 activity represented quantitative end point biomarkers. Study Outcome: Treatment with DF at cytostatic concentrations induced S phase arrest and inhibited RB signaling via downregulated expression of cyclin E, CDK2, pRB and E2F1. DF treatment also induced caspase 3/7 activity, a marker for cellular apoptosis. Collectively, these data provide potential mechanistic leads for anti-proliferative and pro-apoptotic effects of DF in the present model. Conclusion: Present data validate a mechanism-driven experimental approach to prioritize efficacious nutritional herbs as testable alternatives for prevention/therapy of TNBC. Citation Format: Nitin TELANG, Hareesh Nair, George Wong. Drynaria fortunie, a nutritional herb for prevention in triple negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-08-09.

Natural products as drug candidates for breast cancer (Review).

Progression of early-stage breast cancer to advanced-stage metastatic disease represents a major cause of death in women. Long-term conventional and targeted therapy for breast cancer includes multi-drug combinations of cytotoxic chemotherapeutics and pathway-selective small molecule inhibitors. These treatment options are frequently associated with systemic toxicity, intrinsic/acquired therapy resistance and emergence of a drug-resistant cancer stem cell population. This stem cell population has a chemo-resistant, cancer-initiating, premalignant phenotype that is accompanied by cellular plasticity and metastatic potential. These limitations emphasize an unmet need to identify testable alternatives against therapy-resistant metastatic breast cancer. Natural products such as dietary phytochemicals, nutritional herbs and their constitutive bioactive agents have documented human consumption, and lack detectable systemic toxicity and resultant off-target unfavorable side effects. Because of these advantages, natural products may represent testable alternatives for therapy-resistant breast cancer. The present review discusses published evidence for growth inhibitory efficacy of natural products on cellular models for molecular subtypes of clinical breast cancer and development of drug-resistant stem cell models. Collectively, this evidence validates mechanism-based experimental approaches to screen and prioritize efficacious bioactive agents from natural products as novel drug candidates that may function as therapeutic alternatives for breast cancer.

Multivariate Analysis of Tridoshagna Varga of Sidhhamantra Nighantu

Sidhhamantra Nighantu is one such unique lexicon which has a chapter named as Tridoshaghna Varga which enlists the drugs which pacify one, two or all the three Doshas i.e., Vata, Pitta and Kapha. Drugs pacifying all the three Doshas are unique in their Rasa Panchaka in terms of specific combination of Rasa, Guna, Virya and Vipaka. The Tridoshaghna concept and this chapter both stand unique and hence the present chapter was selected for its exploration through multiple correspondence analysis. Materials and Methods: All the relevant information about the drugs like their Botanical identity, family, Rasa, Guna, Virya and Vipaka of Tridoshaghna varga was collected with the help of previous and successive texts of Sidhhamantra Nighantu. The collected information was subjected to multiple correspondence analysis. Result: The chapter Tridoshaghna Varga enlists several substances of herbal origin, metallic/mineral origin and animal origin. MCA revealed that the combination of Sheeta Virya and Madhura Vipaka with the combination of Tikta and/or Katu Rasa can be the best properties for Tridoshaghna action in majority diseased conditions. Conclusion: The study data should be considered while clinical practice by clinicians and further studies should be carried out on the nutritional foods included in the chapter for better understanding of Aahara (nutritional herbs) as well as Aushadha (medicinal herbs) for Tridoshaghna action.

Drug-resistant Stem Cell Models for the Hormone-responsive Luminal A Breast Cancer

Background: Progression of early stage breast cancer to advanced stage metastatic disease represents a major cause of death in women. The Luminal A breast cancer subtype exhibits acceptable response to Chemo-endocrine and targeted therapy. However, these treatment options are associated with intrinsic/acquired therapy resistance and emergence chemo-resistant cancer initiating stem cell population, and resultant progression to advanced stage metastatic disease. These limitations emphasize an unmet need for the development of reliable models for cancer stem cells that facilitate identification of efficacious therapeutic alternatives. Documented human consumption, low systemic toxicity, preclinical cancer growth inhibitory efficacy and stem cell targeting efficacy of natural products, such as dietary phytochemicals and nutritional herbs, provide mechanistic leads for these agents as testable therapeutic alternatives. Objectives: The objectives of the present review are to i.) Provide a systematic discussion of published evidence relevant conceptual background of conventional/targeted therapy and nutritional herbs as testable alternatives, ii.) Growth inhibitory efficacy of nutritional herbs in a cellular model for the Luminal A breast cancer, iii.) Breast cancer stem cell biology and stem cell models for therapy-resistant breast cancer, and iv.) Future research directions. Conclusions: Collectively, all the elements discussed in the present review validate mechanism-based experimental approaches to identify and prioritize potential therapeutic alternatives. Future Research: This review provides a rationale for investigations on patient-derived tumor samples that may minimize extrapolation of the preclinical data for their clinical relevance and translatability.

Stem Cell Models for Breast and Colon Cancer: Experimental Approach for Drug Discovery.

The progression of the early stages of female breast and colon cancer to metastatic disease represents a major cause of mortality in women. Multi-drug chemotherapy and/or pathway selective targeted therapy are notable for their off-target effects and are associated with spontaneous and/or acquired chemotherapy resistance and the emergence of premalignant chemo-resistant cancer-initiating stem cells. The stem cell populations are responsible for the evolution of therapy-resistant metastatic disease. These limitations emphasize an unmet need to develop reliable drug-resistant cancer stem cell models as novel experimental approaches for therapeutic alternatives in drug discovery platforms. Drug-resistant stem cell models for breast and colon cancer subtypes exhibit progressive growth in the presence of cytotoxic chemo-endocrine therapeutics. The resistant cells exhibit upregulated expressions of stem cell-selective cellular and molecular markers. Dietary phytochemicals, nutritional herbs and their constituent bioactive compounds have documented growth inhibitory efficacy for cancer stem cells. The mechanistic leads for the stem cell-targeted efficacy of naturally occurring agents validates the present experimental approaches for new drug discovery as therapeutic alternatives for therapy-resistant breast and colon cancer. The present review provides a systematic discussion of published evidence on (i) conventional/targeted therapy for breast and colon cancer, (ii) cellular and molecular characterization of stem cell models and (iii) validation of the stem cell models as an experimental approach for novel drug discovery of therapeutic alternatives for therapy-resistant cancers.

The Divergent Effects of Ovarian Steroid Hormones in the MCF-7 Model for Luminal A Breast Cancer: Mechanistic Leads for Therapy.

The growth modulating effects of the ovarian steroid hormones 17β-estradiol (E2) and progesterone (PRG) on endocrine-responsive target tissues are well established. In hormone-receptor-positive breast cancer, E2 functions as a potent growth promoter, while the function of PRG is less defined. In the hormone-receptor-positive Luminal A and Luminal B molecular subtypes of clinical breast cancer, conventional endocrine therapy predominantly targets estrogen receptor function and estrogen biosynthesis and/or growth factor receptors. These therapeutic options are associated with systemic toxicity, acquired tumor resistance, and the emergence of drug-resistant cancer stem cells, facilitating the progression of therapy-resistant disease. The limitations of targeted endocrine therapy emphasize the identification of nontoxic testable alternatives. In the human breast, carcinoma-derived hormone-receptor-positive MCF-7 model treatment with E2 within the physiological concentration range of 1 nM to 20 nM induces progressive growth, upregulated cell cycle progression, and downregulated cellular apoptosis. In contrast, treatment with PRG at the equimolar concentration range exhibits dose-dependent growth inhibition, downregulated cell-cycle progression, and upregulated cellular apoptosis. Nontoxic nutritional herbs at their respective maximum cytostatic concentrations (IC90) effectively increase the E2 metabolite ratio in favor of the anti-proliferative metabolite. The long-term exposure to the selective estrogen-receptor modulator tamoxifen selects a drug-resistant phenotype, exhibiting increased expressions of stem cell markers. The present review discusses the published evidence relevant to hormone metabolism, growth modulation by hormone metabolites, drug-resistant stem cells, and growth-inhibitory efficacy of nutritional herbs. Collectively, this evidence provides proof of the concept for future research directions that are focused on novel therapeutic options for endocrine therapy-resistant breast cancer that may operate via E2- and/or PRG-mediated growth regulation.

Anti-Proliferative and Pro-Apoptotic Effects Of Dipsacus Asperoides in a Cellular Model for Triple-Negative Breast Cancer

Background: Triple negative breast cancer (TNBC) lacks expressions of estrogen receptor-α (ER-α), progesterone receptor (PR) and amplified human epidermal growth factor receptor-2 (HER-2). Current treatment for TNBC includes anthracyclin, taxol and cisplatin-based conventional chemotherapy and survival pathway PARP, PI3K, AKT and mTOR selective targeted therapy. These treatments exhibit dose-limiting systemic toxicity and presence of drug resistant cancer stem cells, which highlight the need for identification of efficacious testable alternatives that are not toxic to non-tumorigenic cells. Dipsacus asperoides (DA) is a Chinese nutritional herb and its root represents a common ingredient in Chinese herbal formulations used in women for estrogen related health issues, osteoporosis and breast diseases. This study aims to investigate the growth inhibitory effects of DA, and to detect mechanisms for its efficacy. Methods: Human mammary carcinoma derived triple negative MDA-MB-231 cell line represented the TNBC model. Non-fractionated aqueous extract from DA represented the test agent. Anchorage dependent growth, anchorage independent (AI) colony formation and cell cycle progression quantified growth inhibition. Western blot-based analysis for inhibition of RAS, PI3K and AKT and RB signaling identified mechanistic leads. Results: Treatment with DA induced a dose dependent cytostatic growth arrest (IC50:15 µg/ml; IC90: 30 µg/ml), reduced AI growth and inhibited cell cycle progression via G2/M arrest. DA affected the RAS, PI3K, AKT and RB signaling pathways, and functioned as a natural inhibitor of cyclin dependent kinase 4/6. Cellular apoptosis paralleled increase in pro-apoptotic Caspase 3/7 activity. Conclusion: These results demonstrate that DA inhibited growth, affected cell cycle progression, induced apoptosis and inhibited cancer cell survival pathways. This study validates a mechanism-based approach to identifying testable substitutes for secondary prevention/therapy of TNBC.

Growth inhibitory efficacy of the nutritional herb Psoralea corylifolia in a model of triple‑negative breast cancer

Triple‑negative breast cancer (TNBC) lacks the expression of estrogen receptor‑α (ER‑α), progesterone receptor (PR) and amplified human epidermal growth factor receptor‑2 (HER‑2). Current treatments involve chemotherapy and molecular targeted therapy. These options lead to dose‑limiting systemic toxicity and acquired tumor resistance. Moreover, no drug is yet available for the secondary prevention of TNBC. Such limitations underscore a need to investigate non‑toxic testable alternatives for the secondary prevention/treatment of TNBC. The Chinese nutritional herb, <em>Psoralea corylifolia</em> (PC), has been shown to be effective against the MCF‑7 cell line, a cellular model for ER‑α‑positive breast cancer. The present study aimed to investigate the growth inhibitory effects of PC against TNBC using the MDA‑MB‑231 cell line. Anchorage‑independent colony formation, cell cycle progression, cellular apoptosis, RB signaling and caspase‑3/7 activity assays were performed to determine the quantitative parameters for the efficacy of PC. Treatment with PC induced a 3.5‑fold increase in the G₁: S + G₂/M ratio, an 11‑fold increase in the apoptotic cell number and a 149‑fold increase in caspase‑3/7 activity. PC treatment also decreased cyclin D1, CDK4/6 and p‑RB expression levels. On the whole, the data of the present study identify mechanistic leads for PC as a naturally occurring testable alternative, and validate a mechanistic approach to prioritize efficacious nontoxic herbal extracts as nutritional supplements for the secondary prevention/therapy of TNBC.

Moringa oleifera leaves crude aqueous extract down-regulates of BRCA1, mta-1 and oncogenes c-myc and p53 in AsPC-1, MCF-7 and HTC-116 cells

Moringa oleifera L. (Moringaceae) is a plant used for long time as a nutritional herb as well as for its various pharmacological activities including anticancer activity. Leaves, seed and bark contain active compounds such as phenolic acids, flavonoids, glucosinalates and isocyanates. Despite the extensive literature, the mechanism of action of active compounds still remains unknown. The plant leaves of wild and PMK-1 varieties of Moringa oleifera were extracted by hot water and crude extracts were assessed for their antiproliferative effect on AsPC-1, MCF-7 and HTC116 cells by MTT test. They were found to inhibit MCF-7, HTC116 and AsPC-1 cell proliferation at IC50 of 100, 125 and 240 μg/ml after 72 h of exposure, respectively. The extracts from PMK-1 variety did not show significant inhibition of cell proliferation. Wild type aqueous extract exerted its effect by down-regulation of p53 expression in all cell lines tested and by c-myc down-regulation in AsPC-1 cells. In addition, marker genes of cell lines such as breast cancer 1, early onset (BRCA-1) in MCF-7, metastasis-associated 1 (mta-1) in AsPC-1 and proliferation marker Ki-67 in HTC116 cells have also been down-regulated. The results suggest that polar compounds are involved in exerting these effects and further studies are needed to determine the precise mechanism of action of down-regulation of important genes for cell proliferation.

Phytochemistry and Pharmacology of Moringa Tree: An Overview

Moringa oleifera (M. oleifera) Lam or “kelor”, a common name amongst Indonesian, belongs to the Moringaceae family. It is widely cultivated in India and known as nutritional herbs. Every part of these plants possess a valuable medicinal property. Universally known with the name “horseradish plant” or “drumstick plant” consists of biological exertion such as anticancer, antidiabetic, antihypertensive, treat malnutrition, and beneficial as concentration enhancer and as well as wound healing enterprise. So, the aim of the present review is to present comprehensive information on the traditional uses, phytochemical compound, and pharmacology activities of the medicinal plant, M. oleifera, from recognized sources. In the effort in future studies to develop a novel therapeutic medicine, the information provided in this review will be useful.

Growth inhibitory efficacy of Cornus officinalis in a cell culture model for triple-negative breast cancer.

Triple-negative breast cancer (TNBC) lacks the expressions of estrogen receptor-α, progesterone receptor and human epidermal growth factor receptor-2. The treatment options for TNBC include anthracyclin/taxol based conventional chemotherapy and small molecular inhibitor based targeted therapy. However, the therapeutic efficacy is limited by systemic toxicity and acquired tumor resistance; identification of less toxic testable alternatives is urgently required. Non-toxic nutritional herbs are commonly used in traditional Chinese herbal medicine for general health management and may additionally represent a testable therapeutic alternative for TNBC. The present study examined the growth inhibitory efficacy of the nutritional herb Cornus officinalis (CO) in MDA-MB-231 cells, which represent a cell culture model for TNBC, and identified potential mechanistic leads. In MDA-MB-231 cells, CO induced dose-dependent cytostatic growth arrest [inhibitory concentration (IC)50, 0.1% and IC90, 0.5%], and inhibited anchorage independent colony formation. Mechanistically, CO inhibited G1 to S phase transition leading to G1 arrest and decreased the expression of cyclin D1 and phosphorylated-retinoblastoma proteins. CO additionally altered apoptosis specific BCL-2 associated X protein/B-cell lymphoma-2 expression and upregulated pro-apoptotic caspase-3/7 activity. Collectively, these data provided mechanistic evidence for the efficacy of CO, and validated a mechanism-based approach to prioritize efficacious nutritional herbs as testable alternatives for secondary prevention/treatment of TNBC.

Stem cell targeted therapeutic approaches for molecular subtypes of clinical breast cancer (Review)

The global profiling of differentially expressed genes in subtypes of clinical breast cancer identifies predictive and prognostic biomarkers for disease progression and rationalizes breast cancer subtype‑based treatment options. The expression status of hormone and growth factor receptors dictates the options for chemo‑endocrine and/or pathway selective small molecule inhibitor‑based treatments. Overall, these treatment options are associated with long‑term systemic toxicity and acquired tumor resistance, predominantly due to the emergence of drug‑resistant cancer stem cell population and due to therapy‑resistant disease progression. These limitations emphasize the identification of non‑toxic testable therapeutic alternatives for the efficacious targeting of breast cancer stem cells. The present review summarizes published evidence focused on i) developing cellular models for molecular subtypes of breast cancer; ii) isolating and characterizing drug‑resistant cancer stem cells from the developed models; and iii) identifying mechanistic leads for potential stem cell‑targeting lead compounds. Cellular models for Luminal A, human epidermal growth factor receptor‑2 (HER‑2) enriched and triple‑negative breast cancer subtypes represented the experimental models. Prototypic chemo‑endocrine therapeutic agents were used to select the drug‑resistant stem cell phenotype. The vitamin A derivative, all‑trans retinoic acid, and the rosemary terpenoid, carnosol, respectively representing a mechanistically distinct natural product and a potential bio‑active constituent of a nutritional herb provided stem cell‑selective lead compounds. The cellular models for Luminal A, HER‑2‑enriched and triple‑negative breast cancer subtypes exhibited growth inhibitory effects in response to treatment with prototypic chemo‑endocrine therapeutics, natural products and nutritional herbs. Drug‑resistant phenotypes exhibited an upregulated expression of stem cell‑specific cellular and molecular markers. Lead compounds induced the downregulated expression of the stem cell markers in drug‑resistant phenotypes. These data validate an experimental approach with which to identify potential non‑toxic natural products and nutritional herbs that may represent testable alternatives for the stem cell targeted therapy of breast cancer.

Stem cell targeted therapeutic approaches for molecular subtypes of clinical breast cancer (Review)

The global profiling of differentially expressed genes in subtypes of clinical breast cancer identifies predic‑ tive and prognostic biomarkers for disease progression and rationalizes breast cancer subtype‑based treatment options. The expression status of hormone and growth factor recep‑ tors dictates the options for chemo‑endocrine and/or pathway selective small molecule inhibitor‑based treatments. Overall, these treatment options are associated with long‑term systemic toxicity and acquired tumor resistance, predominantly due to the emergence of drug‑resistant cancer stem cell population and due to therapy‑resistant disease progression. These limitations emphasize the identification of non‑toxic testable therapeutic alternatives for the efficacious targeting of breast cancer stem cells. The present review summarizes published evidence focused on i) developing cellular models for molecular subtypes of breast cancer; ii) isolating and characterizing drug‑resistant cancer stem cells from the developed models; and iii) identi‑ fying mechanistic leads for potential stem cell‑targeting lead compounds. Cellular models for Luminal A, human epidermal growth factor receptor‑2 (HER‑2) enriched and triple‑negative breast cancer subtypes represented the experimental models. Prototypic chemo‑endocrine therapeutic agents were used to select the drug‑resistant stem cell phenotype. The vitamin A derivative, all‑trans retinoic acid, and the rosemary terpenoid, carnosol, respectively representing a mechanistically distinct natural product and a potential bio‑active constituent of a nutritional herb provided stem cell‑selective lead compounds. The cellular models for Luminal A, HER‑2‑enriched and triple‑negative breast cancer subtypes exhibited growth inhibitory effects in response to treatment with prototypic chemo‑endocrine therapeutics, natural products and nutritional herbs. Drug‑resistant phenotypes exhibited an upregulated expression of stem cell‑specific cellular and molecular markers. Lead compounds induced the downregulated expression of the stem cell markers in drug‑resistant phenotypes. These data validate an experimental approach with which to identify potential non‑toxic natural products and nutritional herbs that may represent testable alternatives for the stem cell targeted therapy of breast cancer.

Rhein Induces Cell Death in HepaRG Cells through Cell Cycle Arrest and Apoptotic Pathway.

Rhein, a naturally occurring active anthraquinone found abundantly in various medicinal and nutritional herbs, possesses a wide spectrum of pharmacological effects. Furthermore, previous studies have reported that rhein could induce hepatotoxicity in rats. However, its cytotoxicity and potential molecular mechanisms remain unclear. Therefore, the present study aimed to investigate the cytotoxicity of rhein on HepaRG cells and the underlying mechanisms of its cytotoxicity. Our results demonstrate, by 3-(4,5-dimethyl thiazol-2-yl-)-2,5-diphenyl tetrazolium bromide (MTT) and Annexin V-fluoresce isothiocyanate (FITC)/propidium iodide (PI) double-staining assays, that rhein significantly inhibited cell viability and induced apoptosis in HepaRG cells. Moreover, rhein treatment resulted in the generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential (MMP), and S phase cell cycle arrest. The results of Western blotting showed that rhein treatment resulted in a significant increase in the protein levels of Fas, p53, p21, Bax, cleaved caspases-3, -8, -9, and poly(ADP-ribose)polymerase (PARP). The protein expression of Bcl-2, cyclin A, and cyclin-dependent kinase 2 (CDK 2) was decreased. In conclusion, these results suggest that rhein treatment could inhibit cell viability of HepaRG cells and induce cell death through cell cycle arrest in the S phase and activation of Fas- and mitochondrial-mediated pathways of apoptosis. These findings emphasize the need to assess the risk of exposure for humans to rhein.

Phytochemistry and Pharmacology of Moringa oleifera Lam.

Moringa oleifera Lam. or munga is one of the most important plant widely cultivated in India. It belongs to family Moringaceae. This plant is widely used as nutritional herb and contains valuable pharmacological action like anti-asthmatic, anti-diabetic, hepatoprotective, anti-inflammatory, anti- fertility, anti-cancer, anti-microbial, anti-oxidant, cardiovascular, anti-ulcer, CNS activity, anti-allergic, wound healing, analgesic, and antipyretic activity, Moringa oleifera Lam. The plant is also known as Horse - radish tree, Drumstick tree. Every part of this plant contains a valuable medicinal feature. It contain rich source of the vitamin A, vitamin C and milk protein. Different types of active phytoconstituents like alkaloids, protein, quinine, saponins, flavonoids, tannin, steroids, glycosides, fixed oil and fats are present. This plant is also found in the tropical regions. Some other constituents are niazinin A, niazinin B and niazimicin A, niaziminin B. The present review discusses the phytochemical composition, medicinal uses & pharmacological activity of this plant.

The nutritional herb Epimedium grandiflorum inhibits the growth in a model for the Luminal A molecular subtype of breast cancer.

The Luminal A subtype of breast cancer expresses the estrogen receptor (ER)-α and progesterone receptor (PR), but not the human epidermal growth factor receptor (HER)-2 oncogene. This subtype of breast cancer responds to endocrine therapy involving the use of selective estrogen receptor modulators and/or inhibitors of estrogen biosynthesis. However, these therapeutic agents are frequently associated with long-term systemic toxicity and acquired tumor resistance, emphasizing the need to identify non-toxic alternative treatments for chemo-endocrine therapy responsive breast cancer. The present study utilized the human mammary carcinoma-derived, ER+/PR+/HER-2- MCF-7 cell line as a model of the Luminal A subtype of breast cancer to examine the growth inhibitory effect of the Chinese nutritional herb Epimedium grandiflorum (EG) and determine the mechanisms underlying this effect. MCF-7 cells maintained in a serum-depleted culture medium retained their ability to grow in response to 17β-estradiol (E2). Treatment of the MCF-7 cells with EG resulted in dose-dependent inhibition of E2-promoted growth. Mechanistically, EG inhibited E2-promoted cell cycle progression through G1 stage arrest and modulated the cellular metabolism of E2, increasing the formation of the anti-proliferative metabolites 2-hydroxyestrone and estriol. Long-term treatment of MCF-7 cells with EG inhibited E2-promoted anchorage independent growth, a surrogate in vitro biomarker of tumorigenesis. In conclusion, the results of the present study demonstrate the growth inhibitory effects of EG on MCF-7 cells and identified clinically relevant mechanistic leads for its anti-tumorigenic efficacy.

Inhibitory effects of Chinese nutritional herbs in isogenic breast carcinoma cells with modulated estrogen receptor function.

In estrogen receptor (ER)+ MCF-7 cells, ER represents a ligand-activated transcription factor, and 17β-estradiol (E2) represents its physiological ligand. Maintenance of the human breast carcinoma-derived MCF-7 cells with 0.7% serum selected a proliferative sub-population of E2-responsive cells with transiently non-functional ER due to limited availability of E2. Culture of MCF-7 cells in the presence of either 0.7% serum, <1 nM E2 or 0.7% serum + 20 nM E2 selected isogenic cells with either non-functional ER (ER-NF) or functional ER (ER-F) phenotype. The two phenotypes responded to the growth-promoting effects of E2 and to the growth-inhibitory effects of the selective ER modulator tamoxifen, indicating retention of E2 responsiveness. Comparative dose-response experiments with Chinese nutritional herbs on ER-NF and ER-F cells identified the inhibitory concentration (IC)50 values for these herbs, while the IC50 ratios for the ER-NF:ER-F phenotypes facilitated their rank ordering in terms of efficacy. Out of the 11 efficacious herbs tested, five herbs exhibited ER-F > ER-NF inhibitory activity, four exhibited ER-F = ER-NF inhibitory activity and two exhibited ER-NF > ER-F inhibitory activity. Extracts from representative herbs, Lycium barbarum bark, Epimedium grandiflorum and Cornus officinalis, from each of the three groups inhibited anchorage-independent growth, induced G1 or G2/M arrest and/or apoptosis, and generated anti-proliferative E2 metabolites. The differential growth inhibition in ER-NF and ER-F phenotypes, together with the mechanistic efficacy of representative herbs, identified potential leads for their efficacy on ER+ and/or ER- breast cancer.

Kuppameni: A Potent Herbal Boon for Undernourished Malaysian Indian Plantation Workers

KEYWORDS Herbal Benefit. Plant Extract. Tropical. Nutrient. Alternative Drug ABSTRACT Malaysian Indian plantation workers are economically deprived and suffer from malnutrition. This can be altered by consuming medicinal and nutritional herbs found aplenty in tropical Malaysia. The herb acalypha indica linn, or Indian nettle, which has high antioxidants, is of particular interest for Indian estate workers. Antioxidants in the plant help retard toxic free radicals found in the body. Considered an indigenous form of healthcare, consuming this plant on a regular basis has the potential to rejuvenate the health of the under-nourished Indian plantation worker.

Abstract P4-09-05: Preventive efficacy of the Chinese nutritional herb epimedium grandiflorum in a preclinical cell culture model for luminal A molecular subtype of breast cancer

Abstract Background: The Luminal A molecular sub-type of clinical breast cancer expresses estrogen receptor (ER) and progesterone receptor (PR), but lacks the expression of HER-2 oncogene. This cancer sub-type responds to endocrine therapy involving the use of selective estrogen receptor modulators or inhibitors of estrogen biosynthesis. Conventional therapeutic options are frequently associated with acquired tumor resistance and systemic toxicity, and therefore, emphasize a need for identification of promising new non-toxic agents for secondary prevention. Nutritional substances that do not incur long-term toxicity represent ideal candidates. Nutritional herbs have been used in traditional Chinese medicine for a variety of health related issues, including prevention of breast cancer. Methods: The present study utilized the human mammary carcinoma derived ER+/PR+/HER-2- MCF-7 cells as a model for the Luminal A breast cancer to examine the preventive efficacy of non-fractionated aqueous extract from Epimedium grandiflorum (EG), a popular Chinese nutritional herb. Anchorage dependent growth, cell cycle progression, cellular metabolism of 17b-estradiol (E2), and anchorage independent colony formation represented the quantitative end point biomarkers for preventive efficacy. Results: Maintenance of MCF-7 cells in a chemically defined serum depleted culture medium (serum 0.7%, E2&amp;lt;1 nM) retained their cellular growth promoting response to the physiologically relevant concentration range of 1 nM to 20 nM E2, exhibiting a 10.3% to a 91.9% increase in the viable cell number, respectively. A 7 day treatment of MCF-7 cells with EG resulted in a dose dependent inhibition of E2 promoted growth (EG IC50: 0.49%). At its maximum cytostatic concentration, EG inhibited cell cycle progression via G1 arrest, resulting in a 1.6 fold increase in the G1:S+G2/M ratio, and modulated the cellular metabolism of E2 in favor of formation of anti-proliferative metabolites 2-hydroxyestrone (2-OHE1) and estriol (E3), exhibiting a 5.1 and a 7.6 fold increase, respectively. In addition, EG produced a favorable 3.9 fold increase in the 2-OHE1: 16α-OHE1 ratio, an endocrine biomarker of breast cancer risk. A 21 day treatment of MCF-7 cells with EG produced a dose dependent inhibition in anchorage independent growth (EG IC50: 0.49%; IC90: 1.03%). Conclusions: These data demonstrate the growth inhibitory effects of EG and identify clinically relevant mechanistic leads for its preventive efficacy. The present approach promises to facilitate identification of new efficacious herbs for the secondary prevention of the Luminal A subtype of clinical breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-09-05.