Withanolides
Withania
Medicine, Ayurvedic
Ergosterol
Datura
Dioscoreaceae
Plant Extracts
Withanolide derivatives from the roots of Withania somnifera and their neurite outgrowth activities. (1/77)
Five new withanolide derivatives (1, 9-12) were isolated from the roots of Withania somnifera together with fourteen known compounds (2-8, 13-19). On the basis of spectroscopic and physiochemical evidence, compounds 1 and 9-12 were determined to be (20S,22R)-3 alpha,6 alpha-epoxy-4 beta,5 beta,27-trihydroxy-1-oxowitha-24-enolide (1), 27-O-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside (withanoside VIII, 9), 27-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside (withanoside IX, 10), 27-O-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranoside (withanoside X, 11), and (20R,22R)-1 alpha,3 beta,20,27-tetrahydroxywitha-5,24-dienolide 3-O-beta-D-glucopyranoside (withanoside XI, 12). Of the isolated compounds, 1, withanolide A (2), (20S,22R)-4 beta,5 beta,6 alpha,27-tetrahydroxy-1-oxowitha-2,24-dienolide (6), withanoside IV (14), withanoside VI (15) and coagulin Q (16) showed significant neurite outgrowth activity at a concentration of 1 microM on a human neuroblastoma SH-SY5Y cell line. (+info)Radiosensitizing effect of withaferin A combined with hyperthermia on mouse fibrosarcoma and melanoma. (2/77)
The effect of withaferin A, a plant withanolide, alone or in combination with acute and fractionated radiotherapy and/or hyperthermia, was tested on two mouse tumors, B16F1 melanoma and fibrosarcoma, grown in C57BL and Swiss albino mice, respectively. Tumors were exposed locally to 30 or 50 Gy gamma radiation as acute dose, or 5 fractions of 10 Gy. Withaferin A, 40 mg/kg, was injected intraperitoneally, 1h before acute irradiation, or 30 mg/kg before every 10 Gy fraction. Local hyperthermia, 43 degrees C for 30 min, followed acute RT or first fraction of 10 Gy. Withaferin A, radiation and hyperthermia, individually and in bimodality treatments, produced no complete response (CR) in melanoma. Some CR were seen in fibrosarcoma, which increased after bimodality treatments. Trimodality treatment synergistically increased CR to 37% in melanoma and to 64% in fibrosarcoma. Fractionated radiotherapy (10 Gy x 5) was more effective (25% CR) than acute dose of 50 Gy (0% CR) on melanoma, while there was no difference between the response of fibrosarcoma to the two regimens. Withaferin A with fractionated radiotherapy synergistically increased the CR of both tumors; hyperthermia further enhanced this effect. Utility of withaferin A in increasing the clinical response of radioresistant tumors to fractionated radiotherapy has to be explored. (+info)Development of withaferin A analogs as probes of angiogenesis. (3/77)
The natural product withaferin A (WFA) is a potent angiogenesis inhibitor and it targets the ubiquitin-proteasome pathway in vascular endothelial cells. We generated a biotinylated affinity analog WFA-LC(2)B for use as a probe to study angiogenesis. WFA-LC(2)B inhibits angiogenic sprouting in vitro and it causes levels of ubiquitinated proteins to increase in tumor necrosis factor-alpha-treated human umbilical vein endothelial cells, confirming the retention of WFA's biological activity. We show that WFA-LC(2)B forms protein adducts in endothelial cells which are competed by free WFA in vivo. This WFA-LC(2)B analog will be useful to isolate the biological target of WFA. (+info)Apoptosis is induced in leishmanial cells by a novel protein kinase inhibitor withaferin A and is facilitated by apoptotic topoisomerase I-DNA complex. (4/77)
Protein kinase C (PKC) is an important constituent of the signaling pathways involved in apoptosis. We report here that like staurosporine, withaferin A is a potent inhibitor of PKC. In Leishmania donovani, the inhibition of PKC by withaferin A causes depolarization of DeltaPsim and generates ROS inside cells. Loss of DeltaPsim leads to the release of cytochrome c into the cytosol and subsequently activates caspase-like proteases and oligonucleosomal DNA cleavage. Moreover, in treated cells, oxidative DNA lesions facilitate the stabilization of topoisomerase I-mediated cleavable complexes, which also contribute to DNA fragmentation. However, withaferin A and staurosporine cannot induce cleavable complex formation in vitro with recombinant topoisomerase I nor with nuclear extracts from control cells. Taken together, our results indicate that inhibition of PKC by withaferin A is a central event for the induction of apoptosis and that the stabilization of topoisomerase I-DNA complex is necessary to amplify apoptotic process. (+info)Small molecule anti-angiogenic probes of the ubiquitin proteasome pathway: potential application to choroidal neovascularization. (5/77)
PURPOSE: To characterize the angiogenic and inflammatory responses of human choroidal endothelial cells (HCECs) to stimulators and inhibitors of the ubiquitin proteasome pathway (UPP). METHODS: The regulation of the UPP by the inhibitor withaferin A and its congener, withanolide D, two natural products derived from the medicinal plant Withania somnifera was assessed in the three-dimensional endothelial cell sprouting assay (3D-ECSA), by using HCEC- and human umbilical vein endothelial cell (HUVEC)-derived spheroids embedded in a collagen I matrix. Western blot analysis was used to investigate the effect of withanolides on IkappaB-alpha, polyubiquitination, and heme oxygenase (HO)-1 regulation in HCEC and HUVEC cultures. RESULTS: HCECs, like HUVECs, responded to fibroblast growth factor-2, vascular endothelial growth factor, and tumor necrosis factor (TNF)-alpha stimulation and sprouted vessel-like structures in collagen I matrix. However, HCECs were slower to generate these sprouting vessels, when compared with HUVECs. The extent of inhibition of endothelial cell sprouting in 3D matrix, the blockade of TNF-alpha-induced IkappaB-alpha degradation, levels of global polyubiquitinated proteins, and induced production of HO-1 in response to treatment by the withanolides in cultured endothelial cells was similarly regulated between HCECs and HUVECs. CONCLUSIONS: HCECs share with HUVECs a similar response to UPP inhibitors, suggesting that this well-conserved pathway that regulates angioinflammatory mechanisms could be exploited for drug-targeting in the development of novel agents for CNV treatment. (+info)The tumor proteasome is a primary target for the natural anticancer compound Withaferin A isolated from "Indian winter cherry". (6/77)
Withaferin A (WA) is a steroidal lactone purified from medicinal plant "Indian Winter Cherry" that is widely researched for its variety of properties, including antitumor effects. However, the primary molecular target of WA is unknown. By chemical structure analysis, we hypothesized that Withaferin A might be a natural proteasome inhibitor. Computational modeling studies consistently predict that C1 and C24 of WA are highly susceptible toward a nucleophilic attack by the hydroxyl group of N-terminal threonine of the proteasomal chymotrypsin subunit beta5. Furthermore, WA potently inhibits the chymotrypsin-like activity of a purified rabbit 20S proteasome (IC50=4.5 microM) and 26S proteasome in human prostate cancer cultures (at 5-10 microM) and xenografts (4-8 mg/kg/day). Inhibition of prostate tumor cellular proteasome activity in cultures and in vivo by WA results in accumulation of ubiquitinated proteins and three proteasome target proteins (Bax, p27, and IkappaB-alpha) accompanied by androgen receptor protein suppression (in androgen-dependent LNCaP cells) and apoptosis induction. Treatment of WA under conditions of the aromatic ketone reduction, or reduced form of Celastrol, had significantly decreased the proteasome-inhibitory and apoptosis-inducing activities. Treatment of human prostate PC-3 xenografts with WA for 24 days resulted in 70% inhibition of tumor growth in nude mice, associated with 56% inhibition of the tumor tissue proteasomal chymotrypsinlike activity. Our results demonstrate that the tumor proteasome beta5 subunit is the primary target of WA, and inhibition of the proteasomal chymotrypsin-like activity by WA in vivo is responsible for, or contributes to, the antitumor effect of this ancient medicinal compound. (+info)Withaferin a strongly elicits IkappaB kinase beta hyperphosphorylation concomitant with potent inhibition of its kinase activity. (7/77)
The transcription factor NFkappaB plays a critical role in normal and pathophysiological immune responses. Therefore, NFkappaB and the signaling pathways that regulate its activation have become a major focus of drug development programs. Withania somnifera (WS) is a medicinal plant that is widely used in Palestine for the treatment of various inflammatory disorders. In this study we show that the leave extract of WS, as well as its major constituent withaferin A (WA), potently inhibits NFkappaB activation by preventing the tumor necrosis factor-induced activation of IkappaB kinase beta via a thioalkylation-sensitive redox mechanism, whereas other WS-derived steroidal lactones, such as withanolide A and 12-deoxywithastramonolide, are far less effective. To our knowledge, this is the first communication of IkappaB kinase beta inhibition by a plant-derived inhibitor, coinciding with MEK1/ERK-dependent Ser-181 hyperphosphorylation. This prevents IkappaB phosphorylation and degradation, which subsequently blocks NFkappaB translocation, NFkappaB/DNA binding, and gene transcription. Taken together, our results indicate that pure WA or WA-enriched WS extracts can be considered as a novel class of NFkappaB inhibitors, which hold promise as novel anti-inflammatory agents for treatment of various inflammatory disorders and/or cancer. (+info)Par-4-dependent apoptosis by the dietary compound withaferin A in prostate cancer cells. (8/77)
Deletion or mutation of the androgen receptor (AR) renders prostate tumors refractory to apoptosis by androgen ablation, the mainstay of prostate cancer therapy. To identify novel therapeutics that can induce apoptosis regardless of the AR status of prostate cancer cells, we screened dietary herbal compounds using a reporter assay for the prostate apoptosis response-4 (Par-4) gene, which induces p53- and PTEN-independent and cancer-selective apoptosis. One of the compounds, withaferin A (WA), a major constituent of the dietary compound Withania somnifera, induced Par-4-dependent apoptosis in androgen-refractory prostate cancer cells and regression of PC-3 xenografts in nude mice. Interestingly, restoration of wild-type AR in PC-3 (AR negative) cells abrogated both Par-4 induction and apoptosis by WA. Individually, WA and anti-androgens induced neither Par-4 nor apoptosis in androgen-responsive prostate cancer cells, yet in combination, WA and anti-androgen synergistically induced Par-4 and apoptosis in androgen-responsive prostate cancer cells. Thus, when judiciously combined with anti-androgens, WA inhibits survival of both androgen-responsive and androgen-refractory prostate cancer cells by a Par-4-dependent mechanism. As Par-4 up-regulation induces apoptosis in most tumor cells, our findings can be extended to high-throughput screens to identify synergistic combinations for both therapy-sensitive and therapy-resistant cancers. (+info)Withanolides are a class of steroidal lactones found primarily in the nightshade family of plants, including Ashwagandha (Withania somnifera), a traditional Ayurvedic medicinal plant. These compounds have been reported to possess various pharmacological activities such as anti-inflammatory, antitumor, and immunomodulatory effects. They are currently being researched for their potential uses in various medical applications.
"Withania" is the common name for Withania somnifera, also known as Ashwagandha or Indian ginseng. It is a plant native to India and Southeast Asia that has been used in traditional Ayurvedic medicine for centuries. The root of the plant is used to make medicinal preparations.
Withania somnifera contains several alkaloids, steroidal lactones, and saponins, which are believed to be responsible for its medicinal properties. It has been traditionally used as a remedy for various conditions such as anxiety, insomnia, stress, and inflammation. Some studies suggest that it may have adaptogenic, anti-cancer, anti-inflammatory, and neuroprotective effects, but more research is needed to confirm these findings and establish recommended dosages and safety guidelines.
It's important to note that Withania somnifera supplements can interact with certain medications and have potential side effects, so it's always best to consult a healthcare provider before starting any new supplement regimen.
"Physalis" is a genus name in the plant kingdom, specifically within the Solanaceae family, which also includes tomatoes, potatoes, and bell peppers. It's not typically used in a medical context, but rather in botany and agriculture.
However, certain species of Physalis, like P. alkekengi (Chinese lantern) and P. angulata (wild watermelon), have been used in traditional medicine in various cultures. For instance, the dried fruit of P. alkekengi has been used to treat respiratory ailments in some systems of traditional medicine.
So, a medical definition would be: Physalis is a genus of plants, some species of which have been used in traditional medicine for their perceived therapeutic properties. Please note that these uses are not necessarily supported by scientific evidence and should not be considered as medical advice. Always consult with a healthcare provider for medical concerns.
Ayurvedic medicine, also known as Ayurveda, is a traditional system of medicine that has been practiced in India for thousands of years. It is based on the belief that health and wellness depend on a delicate balance between the mind, body, and spirit. The goal of Ayurvedic medicine is to promote good health, rather than fight disease.
In Ayurveda, each person has a unique constitution, or dosha, that is determined by the balance of three energies: Vata (air and space), Pitta (fire and water), and Kapha (water and earth). These doshas are believed to govern all physical and mental processes and to be responsible for an individual's physical and mental health.
Ayurvedic treatments may include herbal remedies, special diets, detoxification programs, meditation, yoga, and massage therapy. The aim of Ayurvedic medicine is to cleanse the body of toxins, balance the doshas, and promote good health and well-being.
It's important to note that while some people find Ayurvedic practices helpful for maintaining their overall health, there is limited scientific evidence supporting the safety and effectiveness of many Ayurvedic treatments. Additionally, some Ayurvedic products may contain harmful levels of heavy metals, such as lead, mercury, and arsenic, which can be toxic if ingested or absorbed through the skin. It's important to consult with a qualified healthcare provider before starting any new treatment regimen, including Ayurvedic medicine.
Ergosterol is a steroid found in the cell membranes of fungi, which is similar to cholesterol in animals. It plays an important role in maintaining the fluidity and permeability of fungal cell membranes. Ergosterol is also the target of many antifungal medications, which work by disrupting the synthesis of ergosterol or binding to it, leading to increased permeability and eventual death of the fungal cells.
'Datura' is a genus of plants that belong to the family Solanaceae, also known as nightshades. These plants are native to North and South America but have been introduced and naturalized in many parts of the world. Some common names for plants in this genus include Jimson weed, thorn apple, and angel's trumpet.
Datura species contain a variety of toxic alkaloids, including scopolamine, atropine, and hyoscyamine, which can have hallucinogenic effects when ingested. However, these plants are also highly poisonous and can cause serious harm or death if consumed. Ingesting even small amounts can result in symptoms such as dilated pupils, dry mouth, rapid heartbeat, confusion, agitation, and delirium.
It is worth noting that Datura is sometimes used in traditional medicine practices, but it should only be administered under the close supervision of a qualified healthcare provider, as improper use can lead to severe adverse effects.
Aerial parts of plants refer to the above-ground portions of a plant, including leaves, stems, flowers, and fruits. These parts are often used in medicine, either in their entirety or as isolated extracts, to take advantage of their medicinal properties. The specific components of aerial parts that are used in medicine can vary depending on the plant species and the desired therapeutic effects. For example, the leaves of some plants may contain active compounds that have anti-inflammatory or analgesic properties, while the flowers of others may be rich in antioxidants or compounds with sedative effects. In general, aerial parts of plants are used in herbal medicine to treat a wide range of conditions, including respiratory, digestive, and nervous system disorders, as well as skin conditions and infections.
Dioscoreaceae is a family of flowering plants that includes around 750 species, mostly native to tropical and warm temperate regions. It is also known as the yam family. The plants in this family are primarily herbaceous or climbing vines, although some are small trees or shrubs. They have simple, alternate leaves and produce small flowers that are typically greenish-white or yellowish in color.
The most economically important member of Dioscoreaceae is the sweet potato (Ipomoea batatas), which is not a true yam but is a close relative. True yams, on the other hand, are the starchy, tuberous roots of several species of Dioscorea, including D. alata, D. esculenta, and D. rotundata. Yams are an important food crop in many parts of the world, particularly in Africa and Asia.
Overall, Dioscoreaceae is a diverse family of plants that includes a number of economically and culturally significant species.
A plant extract is a preparation containing chemical constituents that have been extracted from a plant using a solvent. The resulting extract may contain a single compound or a mixture of several compounds, depending on the extraction process and the specific plant material used. These extracts are often used in various industries including pharmaceuticals, nutraceuticals, cosmetics, and food and beverage, due to their potential therapeutic or beneficial properties. The composition of plant extracts can vary widely, and it is important to ensure their quality, safety, and efficacy before use in any application.
Molecular structure, in the context of biochemistry and molecular biology, refers to the arrangement and organization of atoms and chemical bonds within a molecule. It describes the three-dimensional layout of the constituent elements, including their spatial relationships, bond lengths, and angles. Understanding molecular structure is crucial for elucidating the functions and reactivities of biological macromolecules such as proteins, nucleic acids, lipids, and carbohydrates. Various experimental techniques, like X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and cryo-electron microscopy (cryo-EM), are employed to determine molecular structures at atomic resolution, providing valuable insights into their biological roles and potential therapeutic targets.
Extract2
- When choosing an ashwagandha product , look for a root powder or a root extract containing, respectively, at least 0.3% and 1.5% of withanolides - key marker compounds which may also play a role in the herb's activity. (consumerlab.com)
- Its unique selling point is the use of Ashwagandha extract standardized to 5% withanolides, which are the active compounds within Ashwagandha. (athleticinsight.com)
Withania1
- This paper describes a method for separation, identification, and quantification of selected withanolides in Withania somnifera plant extracts by HPLC-UV(DAD)-Mass Spectrometry (HPLC-MS). Withaferin-A (WS-3), 12-deoxywithastramonolide (WS-12DS), Withanolide A (WS-1), and Withanone (WS-2) were used as external standards. (csircentral.net)
Compounds6
- Withanolides are a class of compounds found in the ashwagandha plant that have been shown to have numerous potential health benefits. (atlasbars.com)
- Planetary Herbals Ashwagandha is a natural, organic supplement that contains withanolides and other beneficial compounds found in the ashwagandha plant. (atlasbars.com)
- The primary active components in Ashwagandha are a group of chemical compounds called withanolides. (lifevantage.com)
- These effects are often attributed to the active compounds, particularly withanolides, found in Ashwagandha. (bettertogether.org)
- It uses a unique dairy-free process that concentrates the key compounds-called withanolides-to seven times the level of ordinary extracts. (europharmausa.com)
- Compounds 1 and 6 were rare 1-10 seco withanolides. (bvsalud.org)
Ashwagandha supplements1
- Here, we will explore the science behind withanolides and their significance in ashwagandha supplements. (atlasbars.com)
Physalis3
- Isolation and characterisation of irinans, androstane-type withanolides from Physalis peruviana L. (beilstein-journals.org)
- Withanolides from Physalis peruviana . (beilstein-journals.org)
- Six new withanolides, angulasteroidins A-F (1-6), along with twelve known analogs (7-18) were isolated from the whole plants of Physalis angulata. (bvsalud.org)
Ingredients1
- The active chemical ingredients are known as withanolides. (msdmanuals.com)
Alkaloids2
- A natural source of alkaloids and sitoindosides, ashwagandha is perhaps best known for the phytoconstituents withanolides and withaferins, which have been extensively explored for their adaptogenic and rejuvenating properties. (banyanbotanicals.com)
- Traditionally, all parts of the plant were used as medicine, but the root, which has a damp-horse smell, is most commonly used today.Ashwagandha contains at least 26 bioactive alkaloids and steroidal lactones called withanolides. (bayho.com)
Anti-inflammatory3
- Another study found that withanolides have anti-inflammatory properties, which could help reduce chronic inflammation throughout the body. (atlasbars.com)
- Furthermore, withanolides have been found to have anti-inflammatory properties, which can also contribute to reducing stress and anxiety. (atlasbars.com)
- Furthermore, withanolides have also been shown to have anti-inflammatory effects. (atlasbars.com)
Additionally1
- Additionally, withanolides have been found to have potential anti-cancer properties. (atlasbars.com)
Mood1
- By reducing inflammation, withanolides may help to improve overall mood and reduce feelings of stress and anxiety. (atlasbars.com)
Beneficial1
- It contains active components like 'Withanolides' and 'Withaferin' which are very beneficial for nervous system. (planetayurveda.com)
STRENGTH1
- Among these, one product was selected as a Top Pick , offering superior strength and at low cost for withanolides. (consumerlab.com)
Stress3
- One study found that withanolides work as adaptogens in the body, helping to balance hormone levels and reduce stress and anxiety. (atlasbars.com)
- Research has shown that withanolides may have an adaptogenic effect on the body, meaning that they help the body to better cope with stress. (atlasbars.com)
- By reducing cortisol levels (the hormone associated with stress), withanolides may help to promote feelings of calmness and relaxation, making it an effective natural remedy for fighting stress and anxiety. (atlasbars.com)
Plant1
- Immune modulation enables a specialist insect to benefit from antibacterial withanolides in its host plant. (mpg.de)
Found3
- The answer lies in the withanolides found in Planetary Herbals Ashwagandha. (atlasbars.com)
- Withanolides have been found to have immune-boosting properties. (atlasbars.com)
- One study found that withanolides helped to increase the activity of natural killer cells, which are responsible for fighting off infections and illnesses. (atlasbars.com)
Amount1
- The amount of withanolides in a suggested daily serving ranged from just 0.57 mg to as much as 95.3 mg. (consumerlab.com)
Natural1
- While more research is needed in this area, these findings suggest that withanolides could be a promising natural treatment option for certain types of cancer. (atlasbars.com)
Activity of withanolides1
- 3. COVID19-inhibitory activity of withanolides involves targeting of the host cell surface receptor ACE2: insights from computational and biochemical assays. (nih.gov)
Bioactive2
- Its primary bioactive phytonutrient compounds, withanolides, have been shown in research to activate receptors of GABA 2 -the brain's primary inhibitory neurotransmitter. (mindbodygreen.com)
- It contains several bioactive compounds, including a group of substances known as withanolides. (nih.gov)
Withania Somnifera3
- This paper describes a method for separation, identification, and quantification of selected withanolides in Withania somnifera plant extracts by HPLC-UV(DAD)-Mass Spectrometry (HPLC-MS). Withaferin-A (WS-3), 12-deoxywithastramonolide (WS-12DS), Withanolide A (WS-1), and Withanone (WS-2) were used as external standards. (unboundmedicine.com)
- Withanolides, and in particular extracts from Withania somnifera, have been used for over 3,000 years in traditional Ayurvedic and Unani Indian medical systems as well as within several other Asian countries. (nih.gov)
- 1. Subcritical water extraction of withanosides and withanolides from ashwagandha (Withania somnifera L) and their biological activities. (nih.gov)
Iochroma2
- A variety of withanolides and hydroxycinnamic acid amides have been isolated from Iochroma species. (wikipedia.org)
- Alfonso D, Bernardinelli G, Kapetanidis I (1993) Withanolides from Iochroma coccineum . (springer.com)
Active3
- Gaia Herbs uses Ashwagandha root with guaranteed levels of active withanolides. (goldenneedleonline.com)
- Their mind and memory product Ashwagandha herbal dietary supplements boast the presence of 5% withanolides (the active ingredient in the herb). (prurgent.com)
- The active chemical ingredients are known as withanolides. (msdmanuals.com)
Successfully2
- The method was applied successfully to the detection and quantification of the said withanolides in a number of samples. (unboundmedicine.com)
- Cucurbitacins and withanolides can be successfully developed in combination with known TRAIL agonist have the potential of new cancer combination therapies without major toxicities. (nih.gov)
Source1
- Ashwagandha is a natural source of withanolides and withaferins, which have been extensively studied for their adaptogenic and rejuvenating properties. (banyanbotanicals.com)