Antitumoral activity of different Amaryllidaceae alkaloids: In vitro and in silico assays.

ETHNOPHARMACOLOGY RELEVANCE: The plants of Amaryllidaceae family, such as Amaryllis belladonna L., have been used as herbal remedies for thousands of years to address various disorders, including diseases that might today be identified as cancer. AIM OF THE STUDY: The objective of this work was to evaluate the potential of three Amaryllidaceae alkaloids against four cancer cell lines. MATERIAL AND METHODS: The alkaloids lycorine, 1-O-acetylcaranine, and montanine were evaluated in vitro against colon adenocarcinoma cell line (HCT-116) and breast carcinoma cell lines (MCF-7, MDAMB231, and Hs578T). Computational experiments (target prediction and molecular docking) were conducted to gain a deeper comprehension of possible interactions between these alkaloids and potential targets associated with these tumor cells. RESULTS: Montanine presented the best results against HCT-116, MDAMB231, and Hs578T cell lines, while lycorine was the most active against MCF-7. In alignment with the target prediction outcomes and existing literature, four potential targets were chosen for the molecular docking analysis: CDK8, EGFR, ER-alpha, and dCK. The docking scores revealed two potential targets for the alkaloids with scores similar to co-crystallized inhibitors and substrates: CDK8 and dCK. A visual analysis of the optimal docked configurations indicates that the alkaloids may interact with some key residues in contrast to the other docked compounds. This observation implies their potential to bind effectively to both targets. CONCLUSIONS: In vitro and in silico results corroborate with data literature suggesting the Amaryllidaceae alkaloids as interesting molecules with antitumoral properties, especially montanine, which showed the best in vitro results against colorectal and breast carcinoma. More studies are necessary to confirm the targets and pharmaceutical potential of montanine against these cancer cell lines.

Two new sesterterpenoids from Atractylodes japonica Koidz. ex Kitam.

Two new sesterterpenoids, atractylodes japonica terpenoid acid I (1) and atractylodes japonica terpenoid aldehyde I (2), were isolated from the rhizomes of Atractylodes japonica Koidz. ex Kitam together with ten known compounds (3-12). Their structures were elucidated on the basis of comprehensive spectroscopic analysis (1D/2D NMR, HRESIMS and IR). In addition, all of these isolated compounds were evaluated for their cytotoxic activities against human gastric cancer cell MGC-803 and human hepatocellular cancer cell HepG-2. Most of them exhibited moderate to weak inhibitory effects with IC50 values in the range of 25.15-88.85 µM except for 9-12.

Exploring Anticancer Properties of Medicinal Plants against Breast Cancer by Downregulating Human Epidermal Growth Factor Receptor 2.

Plants have a history of being employed in managing breast cancer. However, no scientific evidence supports the idea that these plants can effectively reduce the level of HER2 expression. In this study, extracts from 10 medicinal plants were evaluated for their anticancer properties against HER2-positive breast cancer cells through various methods, including the SRB assay, comet assay, annexin V-FITC dual staining, and immunoblotting. All extracts exerted antiproliferative activity against HER2-positive breast cancer cells. Furthermore, Terminalia chebula (T. chebula), Berberis aristata (B. aristata), and Mucuna pruriens (M. pruriens) reduced HER2 expression in tested cell lines. In addition, an increased Bax/Bcl-2 ratio was observed after the treatment. A comparative proteomics study showed modulation in the proteome profile of breast cancer cells after treatment with T. chebula, B. aristata, Punica granatum, M. pruriens, and Acorus calamus. Metabolic profiling of lead plants revealed the existence of multiple anticancer compounds. Our study demonstrates the considerable potential of the mentioned plants as innovative therapies for HER2-positive breast cancer.

Anti-tumoral Immunity and Chemo-preventive Effectiveness of Herbal Extracts of Curcumin, Ginger, Clove and Amygdaline in Ehrlich Ascites Carcinoma-Challenging Mice.

BACKGROUND: Due to its systemic toxicity, traditional chemotherapy of tumors is being taken into consideration. Herbal therapy, containing phytochemical polyphenol derivatives such as Curcumin (Cur), Ginger (Gin), Cloves (Clov) and Amygdaline (Amyg), is one of the numerous complementary and alternative approaches as an anti-cancer therapy and holds great promise for cancer chemo-prevention with fewer side effects. AIM: The current study was designated to assess anti-tumoral immunity and anti-cancer and chemo-preventive effectiveness of herbal extracts of Cur, Ginger, Clov and Amyg in Ehrlich Ascites Carcinoma (EAC)-challenging mice. METHODS: Chemo-preventive efficacy of herbal extracts of Cur, Gin, Clov and Amyg were analyzed in vivo by examination of the apoptosis rate of EAC tumor cells by flow cytometry. The total numbers of EAC cells, splenocytes counts and leucocytes count with their differentials relative % in peripheral blood (PB) of EACchallenging mice were investigated. RESULTS: EAC-challenging mice treated with herbal extracts of Cur, Gin, Clov and Amyg showed a marked decline in EAC tumor cell count and a noticeable increase in apoptosis rate of EAC tumor cells, a remarkable decrease in serum level of cancer antigen 125 (CA-125) with an obvious increase in the number of splenocytes comparing to that in EAC-challenging mice treated with PBS alone. Moreover, the data indicated an insignificant change in the total leucocytes count and their differentials relative % of eosinophil, neutrophils, monocytes and lymphocytes in EAC-challenging mice treated with Cur and Amyg, but these parameters were markedly increased in EAC-challenging mice injected with Gin and Clov compared to that in EAC-challenging mice treated with PBS alone. CONCLUSION: To conclude, the herbal extracts of Cur, Gin, Clov and Amyg may have anti-tumoral immunity and anti-cancer potency and potential to reduce the resistance to cancer conventional chemotherapy and exert cancer chemo-protective approaches with low adverse effects. Further research is necessary to determine the regimen's toxicity on various tissues and organs and to connect the diagnostic and therapeutic approaches used in the regimen's biomedical use.

UHPLC-MS/MS analysis, cytotoxic, enzyme inhibition, and antioxidant properties of Lantana camara L. extracts obtained by conventional and nonconventional methods.

Lantana camara is widely known as a garden plant, but its use for various medicinal purposes is widespread in traditional medicine. In the frame of this study, L. camara was subjected to several different extraction techniques, including supercritical carbon dioxide extraction, accelerated solvent extraction (ASE), homogenizer-assisted extraction, microwave-assisted extraction, ultrasound-assisted extraction, maceration, and Soxhlet extraction. The investigation encompasses the analysis of the chemical composition alongside assessments of biological activities, such as antioxidant and enzyme-inhibition potential and cytotoxicity of the obtained extracts. The obtained results showed that the extract obtained by accelerated-solvent extraction was the richest in the content of total phenols and of individual compounds. Of the 17 components identified in total, hispidulin was detected in the highest concentration (5.43-475.97 mg/kg). In the antioxidant assays, the extracts obtained by accelerated-solvent and microwave extraction possessed the highest level of antioxidant and antiradical protection. All obtained extracts showed enzyme-inhibitory action on amylase, glucosidase, tyrosinase, and cholinesterase, showing a high potential for application against diseases induced by excessive activity of these enzymes. Cytotoxic analysis was performed on normal and tumor cells, whereby the obtained IC50 values were in the range of 7.685-79.26 µg/mL, showing the high cytotoxicity of the obtained extracts. Using Z score analysis, ASE resulted in an optimal combination of tested quality characteristics of the L. camara extracts.

Piperlongumine and its derivatives against cancer: A recent update and future prospective.

Piperlongumine, or piplartine (PL), is a bioactive alkaloid isolated from Piper longum L. and a potent phytoconstituent in Indian Ayurveda and traditional Chinese medicine with a lot of therapeutic benefits. Apart from all of its biological activities, it demonstrates multimodal anticancer activity by targeting various cancer-associated pathways and being less toxic to normal cells. According to their structure-activity relationship (SAR), the trimethylphenyl ring (cinnamoyl core) and 5,6-dihydropyridin-2-(1H)-one (piperdine core) are responsible for the potent anticancer activity. However, it has poor intrinsic properties (low aqueous solubility, poor bioavailability, etc.). As a result, pharmaceutical researchers have been trying to optimise or modify the structure of PL to improve the drug-likeness profiles. The present review selected 26 eligible research articles on PL derivatives published between 2012 and 2023, followed by the preferred reporting items for systematic reviews and meta-analyses (PRISMA) format. We have thoroughly summarised the anticancer potency, mode of action, SAR and drug chemistry of the proposed PL-derivatives against different cancer cells. Overall, SAR analyses with respect to anticancer potency and drug-ability revealed that substitution of methoxy to hydroxyl, attachment of ligustrazine and 4-hydroxycoumarin heterocyclic rings in place of phenyl rings, and attachment of heterocyclic rings like indole at the C7-C8 olefin position in native PL can help to improve anticancer activity, aqueous solubility, cell permeability, and bioavailability, making them potential leads. Hopefully, the large-scale collection and critical drug-chemistry analyses will be helpful to pharmaceutical and academic researchers in developing potential, less-toxic and cost-effective PL-derivatives that can be used against different cancers.

Mechanism Research of PZD Inhibiting Lung Cancer Cell Proliferation, Invasion, and Migration based on Network Pharmacology.

BACKGROUND: A classic Chinese medicine decoction, Pinellia ternata (Thunb.) Breit.-Zingiber officinale Roscoe (Ban-Xia and Sheng-Jiang in Chinese) decoction (PZD), has shown significant therapeutic effects on lung cancer. OBJECTIVE: This study aimed to explore and elucidate the mechanism of action of PZD on lung cancer using network pharmacology methods. METHODS: Active compounds were selected according to the ADME parameters recorded in the TCMSP database. Potential pathways related to genes were identified through GO and KEGG analysis. The compoundtarget network was constructed by using Cytoscape 3.7.1 software, and the core common targets were obtained by protein-protein interaction (PPI) network analysis. Batch molecular docking of small molecule compounds and target proteins was carried out by using the AutoDock Vina program. Different concentrations of PZD water extracts (10, 20, 40, 80, and 160 µg/mL) were used on lung cancer cells. Moreover, MTT and Transwell experiments were conducted to validate the prominent therapeutic effects of PZD on lung cancer cell H1299. RESULTS: A total of 381 components in PZD were screened, of which 16 were selected as bioactive compounds. The compound-target network consisting of 16 compounds and 79 common core targets was constructed. MTT experiment showed that the PZD extract could inhibit the cell proliferation of NCI-H1299 cells, and the IC50 was calculated as 97.34 ± 6.14 µg/mL. Transwell and wound-healing experiments showed that the PZD could significantly decrease cell migration and invasion at concentrations of 80 and 160 µg/mL, respectively. The in vitro experiments confirmed that PZD had significant therapeutic effects on lung cancer cells, mainly through the PI3K/AKT signaling pathway. CONCLUSION: PZD could inhibit the cell proliferation, migration, and invasion of NCI-H1299 cells partially through the PI3K/AKT signaling pathway. These findings suggested that PZD might be a potential treatment strategy for lung cancer patients.

Investigating the anti-cancer compounds from Calliandra harrisii for precision medicine in pancreatic cancer via in-silico drug design and GC-MS analysis.

Pancreatic cancer is a fatal illness caused by mutations in multiple genes. Pancreatic cancer damages the organ that helps in digestion, resulting in symptoms including fatigue, bloating, and nausea. The use of medicinal plants has been crucial in the treatment of numerous disorders. The medicinal plant Calliandra Harrisi has been widely exploited for its possibilities in biology and medicine. The current study aimed to assess the biopotential of biologically active substances against pancreatic cancer. The GC-MS data of these phytochemicals from Calliandra Harrisi were further subjected to computational approaches with pancreatic cancer genes to evaluate their potential as therapeutic candidates. Molecular docking analysis revealed that N-[Carboxymethyl] maleamic acid is the leading molecule responsible for protein denaturation inhibition, having the highest binding affinity of 6.8 kJ/mol among all other compounds with KRAS inflammatory proteins. Furthermore, ADMET analysis and Lipinski's rule validation were also performed revealing its higher absorption in the gastrointestinal tract. The results of the hepatotoxicity test demonstrated that phytochemicals are non-toxic, safe to use, and do not cause necrosis, fibrosis, or vacuolar degeneration even at excessive levels. Calliandra Harrisi has phytoconstituents that have a variety of pharmacological uses in consideration.

Identifying Anti-NSCLC Bioactive Compounds in Scutellaria via 2D NMR-Based Metabolomic Analysis of Pharmacologically Classified Crude Extracts.

We presented a strategy utilizing 2D NMR-based metabolomic analysis of crude extracts, categorized by different pharmacological activities, to rapidly identify the primary bioactive components of TCM. It was applied to identify the potential bioactive components from Scutellaria crude extracts that exhibit anti-non-small cell lung cancer (anti-NSCLC) activity. Four Scutellaria species were chosen as the study subjects because of their close phylogenetic relationship, but their crude extracts exhibit significantly different anti-NSCLC activity. Cell proliferation assay was used to assess the anti-NSCLC activity of four species of Scutellaria. 1H-13C HSQC spectra were acquired for the chemical profiling of these crude extracts. Based on the pharmacological classification (PCA, OPLS-DA and univariate hypothesis test) were performed to identify the bioactive constituents in Scutellaria associated with the anti-NSCLC activity. As a result, three compounds, baicalein, wogonin and scutellarin were identified as bioactive compounds. The anti-NSCLC activity of the three potential active compounds were further confirmed via cell proliferation assay. The mechanism of the anti-NSCLC activity by these active constituents was further explored via flow cytometry and western blot analyses. This study demonstrated 2D NMR-based metabolomic analysis of pharmacologically classified crude extracts to be an efficient approach to the identification of active components of herbal medicine.

Wighteone, a prenylated flavonoid from licorice, inhibits growth of SW480 colorectal cancer cells by allosteric inhibition of Akt.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice is a frequently used herbal medicine worldwide, and is used to treat cough, hepatitis, cancer and influenza in clinical practice of traditional Chinese medicine. Modern pharmacological studies indicate that prenylated flavonoids play an important role in the anti-tumor activity of licorice, especially the tumors in stomach, lung, colon and liver. Wighteone is one of the main prenylated flavonoids in licorice, and its possible effect and target against colorectal cancer have not been investigated. AIM OF THE STUDY: This study aimed to investigate the anti-colorectal cancer effect and underlying mechanism of wighteone. MATERIALS AND METHODS: SW480 human colorectal cancer cells were used to evaluate the in vitro anti-colorectal cancer activity and Akt regulation effect of wighteone by flow cytometry, phosphoproteomic and Western blot analysis. Surface plasmon resonance (SPR) assay, molecular docking and dynamics simulation, and kinase activity assay were used to investigate the direct interaction between wighteone and Akt. A nude mouse xenograft model with SW480 cells was used to verify the in vivo anti-colorectal cancer activity of wighteone. RESULTS: Wighteone inhibited phosphorylation of Akt and its downstream kinases in SW480 cells, which led to a reduction in cell viability. Wighteone had direct interaction with both PH and kinase domains of Akt, which locked Akt in a "closed" conformation with allosteric inhibition, and Gln79, Tyr272, Arg273 and Lys297 played the most critical role due to their hydrogen bond and hydrophobic interactions with wighteone. Based on Akt overexpression or activation in SW480 cells, further mechanistic studies suggested that wighteone-induced Akt inhibition led to cycle arrest, apoptosis and autophagic death of SW480 cells. Moreover, wighteone exerted in vivo anti-colorectal cancer effect and Akt inhibition activity in the nude mouse xenograft model. CONCLUSION: Wighteone could inhibit growth of SW480 cells through allosteric inhibition of Akt, which led to cell cycle arrest, apoptosis and autophagic death. The results contributed to understanding of the anti-tumor mechanism of licorice, and also provided a rationale to design novel Akt allosteric inhibitors for the treatment of colorectal cancer.

Natural products and derivatives for breast cancer treatment: From drug discovery to molecular mechanism.

BACKGROUND: Breast cancer stands as the most common malignancy among women globally and a leading cause of cancer-related mortality. Conventional treatments, such as surgery, hormone therapy, radiotherapy, chemotherapy, and small-molecule targeted therapy, often fall short of addressing the complexity and heterogeneity of certain breast cancer subtypes, leading to drug resistance and metastatic progression. Thus, the search for novel therapeutic targets and agents is imperative. Given their low toxicity and abundant variety, natural products and their derivatives are increasingly considered valuable sources for small-molecule anticancer drugs. PURPOSE: This review aims to elucidate the pharmacological impacts and underlying mechanisms of active compounds found in select natural products and their derivatives, primarily focusing on breast cancer treatment. It intends to underscore the potential of these substances in combating breast cancer and guide future research directions for the development of natural product-based therapeutics. METHODS: We conducted comprehensive searches in electronic databases such as PubMed, Web of Science, and Scopus until October 2023, using keywords such as 'breast cancer', 'natural products', 'derivatives', 'mechanism', 'signaling pathways', and various keyword combinations. RESULTS: The review presents a spectrum of phytochemicals, including but not limited to flavonoids, polyphenols, and alkaloids, and examines their actions in various animal and cellular models of breast cancer. The anticancer effects of these natural products and derivatives are manifested through diverse mechanisms, including induction of cell death via apoptosis and autophagy, and suppression of tumor angiogenesis. CONCLUSION: An increasing array of natural products and their derivatives are proving effective against breast cancer. Future therapeutic strategies can benefit from strategic enhancement of the anticancer properties of natural compounds, optimization for targeted action, improved bioavailability, and minimized side effects. The forthcoming research on natural products should prioritize these facets to maximize their therapeutic potential.

Multi-targeted therapeutic potential of stigmasterol from the Euphorbia ammak plant in treating lung and breast cancer.

Cancer is the most prevalent disease globally, which presents a significant challenge to the healthcare industry, with breast and lung cancer being predominant malignancies. This study used RNA-seq data from the TCGA database to identify potential biomarkers for lung and breast cancer. Tumor Necrosis Factor (TNFAIP8) and Sulfite Oxidase (SUOX) showed significant expression variation and were selected for further study using structure-based drug discovery (SBDD). Compounds derived from the Euphorbia ammak plant were selected for in-silico study with both TNFAIP8 and SUOX. Stigmasterol had the greatest binding scores (normalized scores of -8.53 kcal/mol and -9.69 kcal/mol) with both proteins, indicating strong stability in their binding pockets throughout the molecular dynamics' simulation. Although Stigmasterol first changed its initial conformation (RMSD = 0.5 nm with the starting conformation) in SUOX, it eventually reached a stable conformation (RMSD of 1.5 nm). The compound on TNFAIP8 showed a persistent shape (RMSD of 0.35 nm), indicating strong protein stability. The binding free energy of the complex was calculated using the MM/GBSA technique; TNFAIP8 had a ΔGTOTAL of -24.98 kcal/mol, with TYR160 being the most significant residue, contributing -2.52 kcal/mol. On the other hand, the SUOX complex had a binding free energy of -16.87 kcal/mol, with LEU151 being the primary contributor (-1.17 kcal/mol). Analysis of the complexes' free energy landscape unveiled several states with minimum free energy, indicating robust interactions between the protein and ligand. In its conclusion, this work emphasises the favourable ability of Stigmasterol to bind with prospective targets for lung and breast cancer, indicating the need for more experimental study.

Alliaxylines A-E: five new mexicanolides from the stem barks of Dysoxylum alliaceum (Blume) Blume ex A.Juss.

A total of five new mexicanolides (1-5), namely alliaxylines A-E, together with two known limonoids 6 and 7, were isolated and identified from Dysoxylum alliaceum (Blume) Blume ex. A.Juss. (Meliaceae). The structures of these compounds were elucidated based on extensive spectroscopic analyses, including HR-ESI-MS, UV, IR, 1D, and 2D NMR, as well as theoretical stimulation of NMR shifts with the DP4 + algorithm. Consequently, this study aimed to examine cytotoxic activities of these compounds against MCF-7 and A549 cell lines. The results implied that compound 2 was the most potent against the two tested cells, with IC50 values of 34.95 ± 0.21 and 44.39 ± 1.03 µM.

A new 3,4-seco-isopimarane and three new isopimarane diterpenoids from Kaempferia champasakensis collected from Vietnam and their cytotoxic activities.

A phytochemical investigation of Kaempferia champasakensis rhizomes led to the isolation of a new 3,4-seco-isopimarane diterpene, kaempferiol A (1), and three new isopimarane diterpenes, kaempferiols B-D (2-4), together with six known isopimarane diterpenes (5-10). The structures of 1-4 were elucidated by extensive spectroscopic analyses, including HR-ESI-MS, UV, IR, and 1D and 2D NMR. The absolute configurations of 1, 3, and 4 were determined by ECD calculations, while that of 2 was established using the modified Mosher method. All isolated compounds were tested for cytotoxicity against three human cancer cell lines, lung cancer (A549), cervical cancer (HeLa), and breast cancer (MCF-7). Among them, 6 and 7 showed moderate cytotoxic activities against the three tested cell lines, with IC50 values ranging from 38.04 to 27.77 µM, respectively.

The pharmacological properties of Gypsophila eriocalyx: The endemic medicinal plant of northern central Turkey.

The aim of this study is to evaluate and compare the biological properties of different extracts (methanol, ethanol, and water) obtained from Gypsophila eriocalyx (G. eriocalyx), a medicinal plant traditionally used in Turkey. The components of different extracts were defined using the GC-MS method. The effects of G. eriocalyx extracts on cell proliferation, apoptosis, and cell cycle arrest in MDA-MB-231 breast cancer as well as in vitro antioxidant, enzyme inhibition, and antimicrobial activities were investigated. In accordance with the results obtained, although ethanol and methanol extracts of G. eriocalyx show higher antioxidant activity than G. eriocalyx water extract, enzyme inhibition activities of the extracts were not found to be significant compared to the reference drug. The methanol and ethanol extract of G. eriocalyx exhibited moderate antimicrobial activity against Staphylococcus aureus and methanol extract showed significant antimicrobial activity against Bacillus cereus. In addition, both extracts significantly inhibited cell viability in a dose-dependent manner in breast cancer cells. The cell growth inhibition by methanol and ethanol extracts induced S phase cell-cycle arrest and apoptosis in MDA-MB-231 cells. Lastly, in order to compare the activities of the chemicals found in Gypsophila eriocalyx plant extract, their activities against various proteins that are breast cancer protein (PDB ID:1A52 and 1JNX), antioxidant protein (PDB ID: 1HD2), AChE enzyme protein (PDB ID: 4M0E), BChE enzyme protein (PDB ID: 5NN0), and Escherichia coli protein (PDB ID: 4PRV)were compared. Then, ADME/T analysis calculations were made to examine the effects of molecules with high activity on human metabolism. Eventually, G. eriocalyx is thought to be a potent therapeutic herb that can be considered as an alternative and functional therapy for the management of diseases of a progressive nature related to oxidative damage such as infection, diabetes, cancer, and Alzheimer's disease.

Investigating the Effects of Dorema hyrcanum Root Extracts on Selective Induction of Programmed Cell Death in Glioblastoma, Ovarian Cancer and Breast Cancer Cell Lines.

BACKGROUND: Despite remarkable advances, cancer has remained the second cause of death, which shows that more potent novel compounds should be found. Ethnobotanical compounds have a long history of treating diseases, and several approved chemotherapeutic compounds were isolated from plants. OBJECTIVE: The research aimed to evaluate the cytotoxic effects of Dorema hyrcanum root extract on ovarian, breast, and glioblastoma cells while examining its selectivity towards normal cells. Additionally, the study is directed to investigate cell death mechanisms, delineate modes of cell death, and explore intracellular ROS production. METHODS: Cytotoxic effects of alcoholic, dichloromethane, and petroleum ether fractions of Dorema hyrcanum were investigated on cancer and normal cells by using MTT assay, and the concentration around IC50 values was used for flow cytometric assessment of apoptosis, evaluation of the expression of selected genes via RT-qPCR and production of ROS. RESULTS: Methanolic extract exhibited the highest cytotoxicity, impacting A2780CP and MDA-MB-231. All fractions showed comparable effects on U251 cells. Notably, extracts displayed higher IC50 values in normal HDF cells, indicating cancer cell specificity. Flow cytometry revealed induction of apoptosis and non-apoptotic death in all three cancer cell lines. QPCR results showed upregulation of related genes, with RIP3K prominently increased in U251 glioblastoma. The DCFH-DA assay demonstrated ROS induction by the PE fraction exclusively in A2780CP cells after 30 minutes and up to 24 hours. CONCLUSION: Dorema hyrcanum root extracts exhibited potent anti-tumor effects against all studied cell lines. The methanolic extract demonstrated the highest cytotoxicity, particularly against A2780CP and MDA-MB-231 cells. Importantly, all fractions displayed selectivity for cancer cells over normal HDF cells. Unique modes of action were observed, with the petroleum ether fraction inducing significant non-apoptotic cell death. These findings suggest promising therapeutic potential for Dorema hyrcanum in cancer treatment with subject to further mechanistic studies.

A Review on the Traditional Applications, Phytochemistry, and Pharmacology of the Genus Physochlaina G. Don.

Physochlaina is a genus of flowering plants belonging to the family Solanaceae and consists of 10 species distributed in various Asian countries. The species of the genus have been traditionally used to cure a variety of illnesses due to their highly valuable medicinal properties, including cancer, asthma, cough, weakness, stomachache, diarrhea, swelling, spasms, toothache, boils, ulcers, rheumatic pain, chronic bronchitis, gastric problems, abdominal pain, palpitation, and insomnia. The species have gained significant attention due to their remarkable ethnopharmacological and ethnomedicinal significance. The researchers have isolated so far 71 biologically active secondary metabolites from different Physochlaina species, which include flavonoids, alkaloids, coumarins, phenolic acids, iridoids, and sterols. These compounds exhibit diverse biological activities, such as antibacterial, anti-oxidant, anti-inflammatory, cytotoxic, and anticancer properties. The present review has been compiled with the intention of providing a comprehensive overview of the botany, distribution, traditional uses, phytochemical profile, and biological activities of the genus Physochlaina for future exploration of plant-based drugs and therapeutic approaches. The present review contributes to understanding the significant pharmacological potential of Physochlaina species and unraveling their chemical composition, highlighting their relevance in developing therapeutic agents. Till date, numerous pharmacological properties and isolated phytochemicals of Physochlaina species that support the species traditional and ethnobotanical history have been documented in a number of scientific publications. However, greater emphasis should be paid to in vivo investigations on various extracts and their phytoconstituents as well as mechanistic analysis to help drug developers better understand how to use Physochlaina species as significant therapeutic resources for herbal formulations using various techniques.

Ginsenoside Rg3: A Review of its Anticancer Mechanisms and Potential Therapeutic Applications.

BACKGROUND: Traditional Chinese Medicine (TCM) has a long history of treating various diseases and is increasingly being recognized as a complementary therapy for cancer. A promising natural compound extracted from the Chinese herb ginseng is ginsenoside Rg3, which has demonstrated significant anticancer effects. It has been tested in a variety of cancers and tumors and has proven to be effective in suppressing cancer. OBJECTIVES: This work covers various aspects of the role of ginsenoside Rg3 in cancer treatment, including its biological functions, key pathways, epigenetics, and potential for combination therapies, all of which have been extensively researched and elucidated. The study aims to provide a reference for future research on ginsenoside Rg3 as an anticancer agent and a support for the potential application of ginsenoside Rg3 in cancer treatment.

Advances in antitumor activity and mechanism of natural steroidal saponins: A review of advances, challenges, and future prospects.

BACKGROUND: Cancer, the second leading cause of death worldwide following cardiovascular diseases, presents a formidable challenge in clinical settings due to the extensive toxic side effects associated with primary chemotherapy drugs employed for cancer treatment. Furthermore, the emergence of drug resistance against specific chemotherapeutic agents has further complicated the situation. Consequently, there exists an urgent imperative to investigate novel anticancer drugs. Steroidal saponins, a class of natural compounds, have demonstrated notable antitumor efficacy. Nonetheless, their translation into clinical applications has remained unrealized thus far. In light of this, we conducted a comprehensive systematic review elucidating the antitumor activity, underlying mechanisms, and inherent limitations of steroidal saponins. Additionally, we propose a series of strategic approaches and recommendations to augment the antitumor potential of steroidal saponin compounds, thereby offering prospective insights for their eventual clinical implementation. PURPOSE: This review summarizes steroidal saponins' antitumor activity, mechanisms, and limitations. METHODS: The data included in this review are sourced from authoritative databases such as PubMed, Web of Science, ScienceDirect, and others. RESULTS: A comprehensive summary of over 40 steroidal saponin compounds with proven antitumor activity, including their applicable tumor types and structural characteristics, has been compiled. These steroidal saponins can be primarily classified into five categories: spirostanol, isospirostanol, furostanol, steroidal alkaloids, and cholestanol. The isospirostanol and cholestanol saponins are found to have more potent antitumor activity. The primary antitumor mechanisms of these saponins include tumor cell apoptosis, autophagy induction, inhibition of tumor migration, overcoming drug resistance, and cell cycle arrest. However, steroidal saponins have limitations, such as higher cytotoxicity and lower bioavailability. Furthermore, strategies to address these drawbacks have been proposed. CONCLUSION: In summary, isospirostanol and cholestanol steroidal saponins demonstrate notable antitumor activity and different structural categories of steroidal saponins exhibit variations in their antitumor signaling pathways. However, the clinical application of steroidal saponins in cancer treatment still faces limitations, and further research and development are necessary to advance their potential in tumor therapy.

New ring-A modified cycloartane triterpenoids from Dysoxylum malabaricum bark: Isolation, structure elucidation and their cytotoxicity.

The Genus Dysoxylum (Meliaceae) consists of approximately 80 species that are abundant in structurally diverse triterpenoids. The present study focused on isolating new triterpenoids from the bark of Dysoxylum malabaricum, one of the predominant species of Dysoxylum present in India. The methanol-dichloromethane bark extract was subjected to LCMS profiling followed by silica gel column chromatography and HPLC analysis to target new compounds. Two new ring A-modified cycloartane-type triterpenoids (1 and 2) were isolated from the bark extract. Spectroscopic methods like NMR, HRESIMS data, and electronic circular dichroism calculations elucidated the structuresandabsolute configurations of the isolated compounds. These compounds were evaluated for their cytotoxic potential against breast cancer cells and displayed notable cytotoxicity. Compound 1 exhibited the highest cytotoxicity against the MDA-MB-231 cells and induced apoptotic cell death. Also, it was able to inhibit glucose uptake and increase nitric oxide production in breast cancer cells.