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Vasorelaxant and antiplatelet agents play an important role in preventing and combating endothelial dysfunction, atherosclerosis and a plethora of associated cardiovascular diseases (CVDs). CVDs are the leading cause of death worldwide and nowadays occur not only in developed but also in developing societies. They include, among others, coronary heart disease, cerebrovascular disease and peripheral artery disease. Due to their high prevalence, it is important to seek efficient preventive measures, such as lifestyle changes and the implementation of appropriate herbal dietary supplementation and treatment alternatives. Plant-derived quinones have recently drawn researchers' attention due to their interesting biological potential. Embelin and rapanone are two plant-derived benzoquinones with anti-inflammatory and antioxidant properties. Embelin has already been shown to have vasorelaxant and antiplatelet activity, but little is known about rapanone in the context of CVDs. Therefore, we decided to comparatively evaluate their activity in a specially designed experimental protocol. Following the isolation of both benzoquinones from plant sources (rapanone from Ardisia crenata leaves; embelin from Lysimachia punctata roots), their effects were comparatively assessed in a biofunctional study on isolated rat aorta (precontracted with phenylephrine) and in vitro on platelet aggregation. Both benzoquinones showed 50% vasorelaxation in an NO-dependent manner. Interestingly, rapanone was slightly more effective as an antiplatelet agent than embelin. The antiplatelet effect of both benzoquinones was specific, as no cytotoxicity towards platelets was observed at the concentrations tested. This is the first report on the vasorelaxant and antiplatelet activity of rapanone. [ABSTRACT FROM AUTHOR]

Genipin is a non-glycosidic iridoid isolated mainly from the fruits of Gardenia jasminoides and Genipa americana. It is the active ingredient in extracts from these plants, responsible for their anti-inflammatory and hepatoprotective effects. In several in vitro tests, its anti-proliferative activity against tumour cell lines has been demonstrated, and due to its ability to specifically inhibit the UCP2 protein and inhibit STAT3 activation, a significant increase in the cytotoxicity of several anticancer drugs was observed in co-treatment with genipin. In recent years, the importance of genipin has increased due to the possibility of using this iridoid as a biocompatible and low cytotoxicity potent crosslinking agent in the manufacture of dressings, in tissue engineering, as a component of a drug carrier system and in the production of food packaging. Genipin is also a substrate in the production of a blue pigment used as a food additive and fabric pigment, and other applications. Due to documented cases of hepatotoxicity, genipin and the blue pigment derived from it are being investigated for effective and safe therapeutic and non-drug use. The current paper discusses selected aspects of chemistry, activity and use of this interesting compound. [ABSTRACT FROM AUTHOR]

Plants from the Amaranthaceae family are a source of oleanolic acid (OA)-type saponins with cytotoxic activity. Two known OA-type saponins, calenduloside E and chikusetsusaponin IVa, were isolated from the roots of Chenopodium strictum Roth. Their structures were confirmed using MS and NMR techniques. This constitutes the inaugural report of the saponins in Ch. strictum. Both the isolated saponins and structurally similar compounds, momordin Ic and OA, were compared for their cytotoxicity against various cancer and normal cell lines (including skin, breast, thyroid, gastrointestinal, and prostate panels). Their effects were dose- and time-dependent, varying with the specific cell line and compound structure. A chemometric approach demonstrated the effects of the compounds on the cell lines. The study discusses the structure–activity observations. The key structural elements for potent cytotoxic activity included the free carboxyl group 28COOH in the sapogenin structure (OA) and the presence of a sugar moiety. The monodesmosides with glucuronic acid (GlcA) at the C3 position of OA were generally more cytotoxic than bidesmosides or OA alone. The addition of xylose in the sugar chain modified the activity towards the cancer cells depending on the specific cell line. OA-type saponins with GlcA (particularly calenduloside E and momordin Ic) represent a promising avenue for further investigation as potential anticancer agents. [ABSTRACT FROM AUTHOR]

This study investigates the phytochemical composition and biological activities of hemp (Cannabis sativa L.) leaves, flowers' methanolic extracts from the Sofia variety, and its sprouts cultivated under different light conditions (natural light, darkness, blue, and white LED light for 5, 7, and 9 days). Phytochemical analysis using HPLC identified four key polyphenolic compounds in sprouts' extracts: chlorogenic, caffeic, and gallic acids, and myricetin, with a predomination of the chlorogenic acid. In contrast, leaves and flowers' extracts contained cannflavins A and B and chlorogenic, p-coumaric, and ferulic acids, with a significant presence of isochlorogenic acid. Antioxidant capacity, assessed by FRAP method, revealed higher antioxidant potential in leaves compared to flowers and sprouts, with sprouts grown under blue and white LED lights exhibiting the highest activity. Cytotoxic activity was evaluated on human colon cancer cell lines (HT29, HCT116, DLD-1) and normal colon epithelial cells (CCD 841 CoN). Results demonstrated significant and selective cytotoxicity against cancer cell lines, with leaves showing more pronounced effects than flowers, and sprouts only moderate activity. All samples revealed an anti-inflammatory effect in vitro. To conclude, sprouts, leaves, and flowers of the Sofia hemp may be considered promising products for chemoprevention in the future. [ABSTRACT FROM AUTHOR]

Introduction: Adaptogens are a group of plants that exhibit complex, nonspecific effects on the human body, increasing its ability to adapt, develop resilience, and survive in stress conditions. They are found in many traditional medicinal systems and play a key role in restoring the body's strength and stamina. Research in recent years has attempted to elucidate the mechanisms behind their pharmacological effects, but it appears that these effects are difficult to define precisely and involve multiple molecular pathways. Neuroinflammation: In recent years, chronic inflammation has been recognized as one of the common features of many central nervous system disorders (dementia and other neurodegenerative diseases, depression, anxiety, ischemic stroke, and infections). Because of the specific nature of the brain, this process is called neuroinflammation, and its suppression can result in an improvement of patients' condition and may promote their recovery. Adaptogens as anti-inflammatory agents: As has been discovered, adaptogens display anti-inflammatory effects, which suggests that their application may be broader than previously thought. They regulate gene expression of anti- and proinflammatory cytokines (prostaglandins, leukotriens) and can modulate signaling pathways (e.g., NF-κB). Aim: This mini-review aims to present the anti-neuroinflammatory potential of the most important plants classified as adaptogens: Schisandra chinensis, Eleutherococcus senticosus, Rhodiola rosea and Withania somnifera. [ABSTRACT FROM AUTHOR]

Melanoma is one of the most dangerous forms of skin cancer, characterized by early metastasis and rapid development. In search for effective treatment options, much attention is given to triterpenoids of plant origin, which are considered promising drug candidates due to their well described anticancer properties and relatively low toxicity. This paper comprehensively summarizes the antimelanoma potential of natural triterpenoids, that are also used as scaffolds for the development of more effective derivatives. These include betulin, betulinic acid, ursolic acid, maslinic acid, oleanolic acid, celastrol and lupeol. Some lesser-known triterpenoids that deserve attention in this context are 22β-hydroxytingenone, cucurbitacins, geoditin A and ganoderic acids. Recently described mechanisms of action are presented, together with the results of preclinical in vitro and in vivo studies, as well as the use of drug delivery systems and pharmaceutical technologies to improve the bioavailability of triterpenoids. This paper also reviews the most promising structural modifications, based on structure–activity observations. In conclusion, triterpenoids of plant origin and some of their semi-synthetic derivatives exert significant cytotoxic, antiproliferative and chemopreventive effects that can be beneficial for melanoma treatment. Recent data indicate that their poor solubility in water, and thus low bioavailability, can be overcome by complexing with cyclodextrins, or the use of nanoparticles and ethosomes, thus making these compounds promising antimelanoma drug candidates for further development. [ABSTRACT FROM AUTHOR]

Benign prostatic hyperplasia (BPH) is a common urological disease affecting aging men. Its pathogenesis is regarded as complex and multifactorial, with sex hormones and inflammation as key contributory factors. In the current study, we investigated the anti-BPH potential of terpenoids present in the fruits of Sorbus intermedia (EHRH.) PERS. Not only the effects on testosterone-stimulated normal prostate epithelial PNT2 cells, namely suppression of 5-α-reductase activity, PSA secretion, and cell proliferation, were determined but also the inhibitory activity on heat-induced protein denaturation, hyaluronidase, as well as IL-6, TNF-α, and NO release in LPS-treated macrophages. Sorbus terpenoids significantly inhibited 5-α-reductase activity and reduced PSA secretion in PNT2 cells, reversing the stimulatory effect of testosterone. PNT2 cell proliferation was also found to be attenuated. Subsequently, all compounds reduced the release of pro-inflammatory mediators in RAW 264.7 cells. In addition, ursolic acid (UA) and its aldehyde (UAL) were the most potent hyaluronidase inhibitors of all compounds, with IC50 values of 225.75 µg/mL and 369.77 µg/mL, respectively. For better understanding and interpretation of the overall effect of Sorbus terpenoids on different aspects of BPH pathogenesis and development, cluster analysis was applied. [ABSTRACT FROM AUTHOR]

Saponins are plant metabolites that possess multidirectional biological activities, among these is antitumor potential. The mechanisms of anticancer activity of saponins are very complex and depend on various factors, including the chemical structure of saponins and the type of cell they target. The ability of saponins to enhance the efficacy of various chemotherapeutics has opened new perspectives for using them in combined anticancer chemotherapy. Co-administration of saponins with targeted toxins makes it possible to reduce the dose of the toxin and thus limit the side effects of overall therapy by mediating endosomal escape. Our study indicates that the saponin fraction CIL1 of Lysimachia ciliata L. can improve the efficacy of the EGFR-targeted toxin dianthin (DE). We investigated the effect of cotreatment with CIL1 + DE on cell viability in a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, on proliferation in a crystal violet assay (CV) and on pro-apoptotic activity using Annexin V/7 Actinomycin D (7-AAD) staining and luminescence detection of caspase levels. Cotreatment with CIL1 + DE enhanced the target cell-specific cytotoxicity, as well as the antiproliferative and proapoptotic properties. We found a 2200-fold increase in both the cytotoxic and antiproliferative efficacy of CIL1 + DE against HER14-targeted cells, while the effect on control NIH3T3 off-target cells was less profound (6.9- or 5.4-fold, respectively). Furthermore, we demonstrated that the CIL1 saponin fraction has a satisfactory in vitro safety profile with a lack of cytotoxic and mutagenic potential. [ABSTRACT FROM AUTHOR]

Inflammation is a response of the organism to an external factor that disrupts its natural homeostasis, and it helps to eliminate the cause of tissue injury. However, sometimes the body's response is highly inadequate and the inflammation may become chronic. Thus, the search for novel anti-inflammatory agents is still needed. One of the groups of natural compounds that attract interest in this context is lichen metabolites, with usnic acid (UA) as the most promising candidate. The compound reveals a broad spectrum of pharmacological properties, among which anti-inflammatory properties have been studied both in vitro and in vivo. The aim of this review was to gather and critically evaluate the results of the so-far published data on the anti-inflammatory properties of UA. Despite some limitations and shortcomings of the studies included in this review, it can be concluded that UA has interesting anti-inflammatory potential. Further research should be directed at the (i) elucidation of the molecular mechanism of UA; (ii) verification of its safety; (iii) comparison of the efficacy and toxicity of UA enantiomers; (iv) design of UA derivatives with improved physicochemical properties and pharmacological activity; and (v) use of certain forms or delivery carriers of UA, especially in its topical application. [ABSTRACT FROM AUTHOR]

Cuphea P. Browne (Lythraceae) is a monophyletic taxon comprising some 240–260 species that grow wild in the warm, temperate, and tropical regions of South and Central America and the southern part of North America. They have been valued as traditional medicinal remedies for numerous indications, including treating wounds, parasitic infections, hypertension, digestive disorders, cough, rheumatism, and pain. Modern pharmacological research provides data that support many of these traditional uses. Such a wide array of medicinal applications may be due to the exceptionally rich phytochemical profile of these plants, which includes bioactive compounds classified into various metabolite groups, such as polyphenols, triterpenes, alkaloids, and coumarins. Furthermore, Cuphea seed oils, containing medium-chain fatty acids, are of increasing interest in various industries as potential substitutes for coconut and palm oils. This review aims to summarize the results of phytochemical and pharmacological studies on Cuphea plants, with a particular focus on the therapeutic potential and molecular mechanisms of the action of polyphenolic compounds (especially flavonoids and tannins), which have been the subject of many recently published articles. [ABSTRACT FROM AUTHOR]

The genus Atriplex provides species that are used as food and natural remedies. In this work, the levels of soluble phenolic acids (free and conjugated) and flavonoids in extracts from roots, stems, leaves and flowers of the unexplored Atriplex sagittata Borkh were investigated by LC-ESI-MS/MS, together with their antioxidant and antihyaluronidase activity. Phenolic acids were present in all parts of A. sagittata; and were most abundant in the leaves (225.24 μg/g dw.), whereas the highest content of flavonoids were found in the flowers (242.71 μg/g dw.). The most common phenolics were 4-hydroxybenzoic and salicylic acids, kaempferol-3-glucoside-7-rhamnoside, kaempferol-3-rutinoside and the rare narcissoside, which was present in almost all morphotic parts. The stem extract had the highest antioxidant activity and total phenolic content (611.86 mg/100 g dw.), whereas flower extract exerted the most potent antihyaluronidase effect (IC50 = 84.67 µg/mL; control—quercetin: IC50 = 514.28 μg/mL). Phytochemical analysis of the flower extract led to the isolation of two triterpene saponins that were shown to be strong hyaluronidase inhibitors (IC50 = 33.77 and 168.15 µg/mL; control—escin: IC50 = 307.38 µg/mL). This is the first report on the presence of phenolics and saponins in A. sagittata. The results suggest that both groups of metabolites may contribute to the overall activity of this plant species. [ABSTRACT FROM AUTHOR]

Abiotic elicitation, a well-known strategy in mushroom biotechnology, promotes increased accumulation of secondary metabolites in mycelial cultures. The study aimed the effects of methyl jasmonate (MeJA) on the production of triterpenes in submerged cultures of Ganoderma applanatum. Further, the study evaluated the cytotoxic activity of the extract corresponding to the optimal elicitation variant in selected human cancer cell lines as well as the selectivity against normal cells. MeJA was added on days 1, 4, 6, and 8 in the 10-day growth cycle at concentrations of 10, 50, 100, 150, and 200 µM MeJA. The HPLC-DAD was used to analyze the triterpenes. The cytotoxic activity was tested using the MTTFc assay in grouped panels of skin, prostate, and gastrointestinal cancer cells. The results of the quantitative analyses confirmed the stimulating effect of MeJA on the production of ganoderic acid A and ganoderic acid C. The greatest increase in total triterpenes was found on day 6 of the culture cycle compared to the control group—with the concentration of MeJA—150 µM. Compared to the control samples, mycelial culture extract after the most productive elicitation variant showed significant cytotoxic activity against prostate cancer cells and moderate effects on melanoma cells. Ganoderma applanatum mycelial cultures can be proposed as a model to study the dynamics of the accumulation of compounds with therapeutic values through abiotic elicitation. [ABSTRACT FROM AUTHOR]

Rapanone is a plant-derived simple alkyl-dihydroxybenzoquinone structurally close to embelin, a well-known cytotoxic agent. The pharmacological characterization of rapanone is still incomplete, and to fill the data gap, a good source for its acquisition is required to conduct further research. This study aimed to optimize the conditions for the extraction of rapanone from the leaves of white-berried Ardisia crenata Sims. For this purpose, three methods were employed: heat reflux (HRE), shaking (SE), and ultrasound-assisted extraction (UAE), and such parameters as the extraction time, solvent, and the number of extractions from the same sample were set as experimental variables. Furthermore, cytotoxic activity toward prostate cancer, thyroid cancer, and colorectal carcinoma cell lines was investigated and compared with doxorubicin and embelin. The most effective and economical method for the extraction of rapanone was shown to be 20 min UAE with ethyl acetate or chloroform. Rapanone exhibited high cytotoxic activity against PC3 (IC50 = 6.50 μg/mL), Du145 (IC50 = 7.68 μg/mL), FTC133 (IC50 = 6.01 μg/mL), 8505C (IC50 = 7.84 μg/mL), and Caco-2 (IC50 = 8.79 μg/mL) cell lines after 24 h and against the HT29 cell line after 48 h (IC50 = 11.67 μg/mL). Furthermore, it revealed a more favorable safety profile than either its homologue, embelin, or doxorubicin. The set of optimal extraction parameters obtained may be utilized for scientific and industrial purposes to achieve the best rapanone yield. Moreover, this benzoquinone revealed a high cytotoxic activity with good selectivity. [ABSTRACT FROM AUTHOR]

The dried Glechoma hederacea L. herb has a long history of use in traditional medicine. Its therapeutic potential is related to the presence of phenolic compounds. To optimize extraction efficiency the effect of the use of different techniques (HRE—heat reflux extraction, I/ME—infusion combined with maceration, UE—sonication and SE—Soxhlet extraction), various solvents (water and ethanol) and processing time (15 min to 2 h) on phenolics content was investigated. The HPLC method was applied to determine and compare the content of phenolic acids (rosmarinic, chlorogenic, protocatechuic) and flavonoids (rutin, isoquercetin) in the extracts. Furthermore, the cytotoxic activity of the extracts was examined for the first time against human cancer and normal cells of skin origin (A375, HTB140, HaCaT) and gastrointestinal origin (Caco-2 and HT-29, HepG2). In addition, the antioxidant potential was evaluated using the DPPH and FRAP method. The I/ME-water and HRE/ethanol procedures turned out to be optimal for obtaining extracts of dried G. hederacea L. herb rich in bioactive phenolics. These extracts exhibited high antioxidant activity, correlated with the content of the compounds analyzed. Furthermore, the extracts of the dried Glechoma herb were not toxic to normal human cells, indicating its safe use both internally and externally. [ABSTRACT FROM AUTHOR]

Despite a significant amount of research, the relationship between a diet rich in isoflavones and breast and prostate cancer risk is still ambiguous. The purpose of the current study was to pre-select the potential candidate for functional foods among red, white, crimson, and Persian clover sprouts, cultured for different periods of time (up to 10 days), with respect to the isoflavone content (determined by HPLC-UV-VIS), and to verify their impact on hormone-dependent cancers in vitro. The red clover sprouts were the richest in isoflavones (up to 426.2 mg/100 g dw), whereas the lowest content was observed for the crimson clover. Each species produced isoflavones in different patterns, which refer to the germination time. Hormone-insensitive MDA-MB-231 breast cancer cells were more resistant to the tested extracts than estrogen-dependent MCF7 breast cancer cells. Regarding prostate cancer, androgen-dependent LNCap cells were most susceptible to the tested sprouts, followed by androgen-insensitive, high metastatic PC3, and low metastatic DU145 cells. The observed cytotoxic impact of the tested sprouts is not associated with isoflavone content, as confirmed by chemometric analysis. Furthermore, the sprouts tested revealed a high antioxidant potential, and were characterized by high safety for normal breast and prostate cells. [ABSTRACT FROM AUTHOR]

Quercetin is one of the most common, naturally occurring flavonoids, structurally classified to the flavonol subfamily. This compound, found in many edible and medicinal plants either as a free or glycosidated form, has been scientifically exploited for many years, and one could hardly expect it could be a hero of some additional story. Commonly recognized as an anti-inflammatory agent, quercetin not only limits capillary vessel permeability by inhibiting hyaluronidase but also blocks cyclooxygenases and lipoxygenases. As a typical flavonoid, it is also known for its antioxidant effect, which was confirmed by many in vitro and in vivo studies. Throughout the years, numerous other activities were reported for quercetin, including antidiabetic, anti-proliferative, or anti-viral. Of note, recent data have revealed its potential role as a therapeutic agent for several central nervous system disorders. This review provides an overview of available experimental data on quercetin and its complexes with respect to central nervous system diseases, with a main focus on some aspects that were not discussed previously, such as anti-anxiolytic effects, anti-Huntington's disease activity, or therapeutic potential in brain cancer. Moreover, quercetin's protective role in some of these diseases is discussed, especially as an anti-neuroinflammatory agent. Bearing in mind the poor bioavailability of this compound, possible options that would enhance its delivery to the site of action are also presented. [ABSTRACT FROM AUTHOR]

The study aimed to examine whether usnic acid—a lichen compound with UV-absorbing properties—can be considered as a prospective photoprotective agent in cosmetic products. Moreover, a comparison of two usnic acid enantiomers was performed to preselect the more effective compound. To meet this aim, an in vitro model was created, comprising the determination of skin-penetrating properties via skin-PAMPA assay, safety assessment to normal human skin cells (keratinocytes, melanocytes, fibroblasts), and examination of photostability and photoprotective properties. Both enantiomers revealed comparable good skin-penetrating properties. Left-handed usnic acid was slightly more toxic to keratinocytes (IC50 80.82 and 40.12 µg/mL, after 48 and 72 h, respectively) than its right-handed counterpart. The latter enantiomer, in a cosmetic formulation, was characterized by good photoprotective properties and photostability, comparable to the UV filter octocrylene. Perhaps most interestingly, (+)-usnic acid combined with octocrylene in one formulation revealed enhanced photoprotection and photostability. Thus, the strategy can be considered for the potential use of (+)-usnic acid as a UV filter in cosmetic products. Moreover, the proposed model may be useful for the evaluation of candidates for UV filters. [ABSTRACT FROM AUTHOR]

Usnic acid (UA) is a chiral lichen metabolite with an interesting pharmacological profile. The aim of this study was to compare the anti-melanoma effect of (+)-UA and (−)-UA in an in vitro model by studying their impact on the cells as well as the processes associated with cancer progression. The effect of UA enantiomers on the viability, proliferation, and invasive potential of three melanoma cell lines (HTB140, A375, WM793) was evaluated. Their interaction with a chemotherapeutic drug—doxorubicin was assessed by isobolographic analysis. Anti-inflammatory and anti-tyrosinase properties of (+)-UA and (−)-UA were also examined. Both UA enantiomers dose- and time-dependently decreased the viability of all three melanoma cell lines. Their synergistic effect with doxorubicin was observed on A375 cells. (+)-Usnic acid at a sub-cytotoxic dose strongly inhibited melanoma cells migration. Both UA enantiomers decreased the release of pro-inflammatory mediators. The cytotoxic effect of (+)-UA and (−)-UA depends greatly on the melanoma cell type; however, the overall anti-melanoma potential is perspective. Our results indicate that the strategy of combining usnic acid enantiomers with cytostatic drugs may be an interesting option to consider in combating melanoma; however, further studies are required. [ABSTRACT FROM AUTHOR]

Two triterpene saponins, including a novel serjanic acid derivative, were isolated from Chenopodium hybridum L. (Amaranthaceae) aerial parts. Their structures were elucidated by a combination of spectroscopic methods (MS, 1D and 2D NMR). Both compounds were evaluated for cytotoxicity and selectivity on skin, prostate, gastrointestinal, thyroid and lung cancer cells. Their effect was dose and time-dependent with varied potency, the highest against prostate PC3 and melanoma WM793, where IC50 was lower than the reference drug doxorubicin. Structure–activity relationship is briefly discussed. [ABSTRACT FROM AUTHOR]

Cannabis sativa L. turned out to be a valuable source of chemical compounds of various structures, showing pharmacological activity. The most important groups of compounds include phytocannabinoids and terpenes. The pharmacological activity of Cannabis (in epilepsy, sclerosis multiplex (SM), vomiting and nausea, pain, appetite loss, inflammatory bowel diseases (IBDs), Parkinson's disease, Tourette's syndrome, schizophrenia, glaucoma, and coronavirus disease 2019 (COVID-19)), which has been proven so far, results from the affinity of these compounds predominantly for the receptors of the endocannabinoid system (the cannabinoid receptor type 1 (CB1), type two (CB2), and the G protein-coupled receptor 55 (GPR55)) but, also, for peroxisome proliferator-activated receptor (PPAR), glycine receptors, serotonin receptors (5-HT), transient receptor potential channels (TRP), and GPR, opioid receptors. The synergism of action of phytochemicals present in Cannabis sp. raw material is also expressed in their increased bioavailability and penetration through the blood–brain barrier. This review provides an overview of phytochemistry and pharmacology of compounds present in Cannabis extracts in the context of the current knowledge about their synergistic actions and the implications of clinical use in the treatment of selected diseases. [ABSTRACT FROM AUTHOR]