| Features: | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Glycyrrhizic acid (GA) is a significant constituent of licorice root. Glycyrrhizin, the main active component obtained from licorice roots, has many pharmacological and biological functions such as protecting liver cells, anti-inflammation, anti-virus, immunomodulation, has been widely applied in the treatment of clinically related hepatic diseases (Dastagir & Rizvi, 2016). Glycyrrhizin is a natural inhibitor of HMGB1 Licorice — Licorice is the dried root and stolon of Glycyrrhiza species, principally Glycyrrhiza glabra, G. uralensis, and G. inflata, used as a botanical medicine and food ingredient. It is a complex phytochemical mixture rather than a single drug. Major bioactive classes include the triterpenoid saponin glycyrrhizin (glycyrrhizic acid), its intestinal metabolite 18β-glycyrrhetinic acid, and numerous flavonoids and chalcones including liquiritigenin, isoliquiritigenin, glabridin, and species-dependent licochalcones. Standard abbreviations include LE for licorice extract and GL for glycyrrhizin. Anticancer findings are predominantly preclinical and depend strongly on species, extract preparation, constituent composition, and concentration. Glycyrrhizin is particularly important because it directly binds and inhibits extracellular HMGB1 signaling, while several flavonoid constituents contribute additional antiproliferative effects. Primary mechanisms (ranked):
Bioavailability / PK relevance: Oral glycyrrhizin has low systemic exposure as intact glycyrrhizin and undergoes extensive metabolism by intestinal microbiota to glycyrrhetinic acid and additional metabolites. In a human study using a 75-mg oral glycyrrhizin dose, mean glycyrrhizin peak plasma concentration was approximately 25 ng/mL while glycyrrhetinic acid reached approximately 200 ng/mL. Consequently, systemic biology after oral licorice can differ markedly from direct exposure experiments using glycyrrhizin or crude extract. Formulation, intestinal microbiota, biliary transport, species of licorice, glycyrrhizin content, and concomitant botanicals can materially alter exposure. In-vitro vs systemic exposure relevance: Many anticancer experiments expose cells directly to licorice extracts or purified constituents at tens to hundreds of µg/mL or micromolar concentrations. These exposures frequently exceed circulating concentrations achievable after conventional oral licorice or glycyrrhizin administration. For example, recent whole-extract studies reported substantial antiproliferative effects around 30–200 µg/mL, whereas orally administered glycyrrhizin produces plasma levels in the ng/mL range and is extensively converted to metabolites. Whole-extract in-vitro anticancer potency should therefore not be interpreted as demonstrating equivalent systemic antitumor exposure in humans. Clinical evidence status: Preclinical for treatment or prevention of cancer. Cell and animal evidence supports several anticancer mechanisms, particularly glycyrrhizin-HMGB1 signaling and constituent-dependent antiproliferative effects. Small human / RCT adjunct evidence exists for supportive care rather than tumor treatment; randomized studies have reported reduced pain and severity of radiotherapy-associated oral mucositis with topical licorice preparations. There is no established clinical evidence that oral licorice treats human malignancy or improves cancer survival. Safety / translation relevance: Glycyrrhizin-containing licorice has a clinically important dose- and duration-dependent mineralocorticoid-like toxicity. Glycyrrhetinic-acid-related metabolites inhibit renal 11β-HSD2, permitting cortisol activation of mineralocorticoid receptors and potentially causing sodium retention, hypertension, edema, hypokalemia, metabolic alkalosis, arrhythmias, and suppression of renin and aldosterone. Risk increases with prolonged exposure and can be influenced by intestinal microbiota, renal/hepatic function, albumin concentration, age, and interacting medications. Licorice can also alter drug metabolism and should not be assumed pharmacologically inert when used with cancer therapy. Licorice Mechanistic Profile
|
| Source: |
| Type: |
| Caspases are a cysteine protease that speed up a chemical reaction via pointing their target substrates following an aspartic acid residue.1 They are grouped into apoptotic (caspase-2, 3, 6, 7, 8, 9 and 10) and inflammatory (caspase-1, 4, 5, 11 and 12) mediated caspases. Caspase-1 may have both tumorigenic or antitumorigenic effects on cancer development and progression, but it depends on the type of inflammasome, methodology, and cancer. Catalase is an enzyme found in nearly all living cells exposed to oxygen. Its primary role is to protect cells from oxidative damage by catalyzing the conversion of hydrogen peroxide (H₂O₂), a potentially damaging byproduct of metabolism, into water (H₂O) and oxygen (O₂). This detoxification process is crucial because excess H₂O₂ can lead to the formation of reactive oxygen species (ROS) that damage proteins, lipids, and DNA. Catalase and Cancer Oxidative Stress and Cancer: Cancer cells often experience increased levels of oxidative stress due to rapid proliferation and metabolic changes. This stress can lead to DNA damage, promoting tumorigenesis. Catalase helps mitigate oxidative stress, and its expression can influence the survival and proliferation of cancer cells. Expression Levels in Different Cancers: Overexpression: In some cancers, such as breast cancer and certain types of leukemia, catalase may be overexpressed. This overexpression can help cancer cells survive in oxidative environments, potentially leading to more aggressive tumor behavior. Downregulation: Conversely, in other cancers, such as colorectal cancer, reduced catalase expression has been observed. This downregulation can lead to increased oxidative stress, contributing to tumor progression and metastasis. Prognostic Implications: Survival Rates: Studies have shown that high levels of catalase expression can be associated with poor prognosis in certain cancers, as it may enable cancer cells to resist apoptosis (programmed cell death) induced by oxidative stress. Some types of cancer cells have been reported to exhibit lower catalase activity, possibly increasing their vulnerability to oxidative damage under certain conditions. This vulnerability has even been exploited in some therapeutic strategies (for example, approaches that generate excess H₂O₂ or other ROS specifically targeting cancer cells have been researched). |
| 8236- | LE, | Licorice (Glycyrrhiza glabra L.)-Derived Phytochemicals Target Multiple Signaling Pathways to Confer Oncopreventive and Oncotherapeutic Effects |
| - | Review, | Var, | NA |
Query results interpretion may depend on "conditions" listed in the research papers. Such Conditions may include : -low or high Dose -format for product, such as nano of lipid formations -different cell line effects -synergies with other products -if effect was for normal or cancerous cells
Filter Conditions: Pro/AntiFlg:% IllCat:% CanType:% Cells:% prod#:115 Target#:46 State#:% Dir#:2
wNotes=0 sortOrder:rid,rpid