The crude ethanolic extract of O. tenuiflorum demonstrated consistent, multi-target bioactivity, combining antioxidant, anti-inflammatory, and cytotoxic effects, supporting its potential as a chemopreventive and therapeutic agent against CRC.
Abstract
Background Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide, with persistent challenges of systemic toxicity, chemoresistance, and limited efficacy of conventional therapies underscoring the need for safer therapeutic alternatives. Ocimum tenuiflorum (Holy Basil), a phytochemically rich medicinal herb with established antioxidant, anti-inflammato Methods An integrated in vitro and in silico approach was employed. The ethanolic extract of O. tenuiflorum leaves was prepared by Soxhlet extraction and evaluated for cytotoxicity (MTT, XTT, LDH release, Trypan Blue exclusion) against HCT116 colorectal cancer cells, antioxidant activity (DPPH, ABTS, FRAP assays), and anti-inflammatory activity (nitric oxide and cyclooxygenase inhibition assays) using RAW 264.7 macrophages. Computational analyses included protein-protein interaction (PPI) network construction via STRING, molecular docking (Glide SP/XP) of bioactive ligands against NF-κB (PDB: 1NFK) and JAK1 (PDB: 5XGJ), a 200 ns molecular dynamics (MD) simulation of the lead complex, and Density Functional Theory (DFT) calculations at the B3LYP/6-31G* level. Results The extract exhibited significant, concentration-dependent cytotoxicity against HCT116 cells (MTT IC50: 70.4 µg/mL), substantial antioxidant activity (DPPH IC50: 34.7 µg/mL), and notable inhibition of nitric oxide and COX activity, indicating modulation of oxidative stress and tumor-associated inflammation. PPI analysis revealed high-connectivity NFKB1 and PIK3CA signaling hubs central to CRC progression. Among all screened phytochemicals, rosmarinic acid demonstrated the highest binding affinity against NF-κB (docking score: −5.898 kcal/mol) and JAK1 (−6.812 kcal/mol), forming a stable complex over the 200 ns MD simulation (backbone RMSD: ±2.7 Å). DFT analysis revealed a moderate HOMO–LUMO gap (3.895 eV), indicating favorable electronic stability and chemical reactivity. Discussion The crude ethanolic extract of O. tenuiflorum demonstrated consistent, multi-target bioactivity, combining antioxidant, anti-inflammatory, and cytotoxic effects, supporting its potential as a chemopreventive and therapeutic agent against CRC. Within this extract, rosmarinic acid emerged as the principal bioactive contributor, exhibiting markedly higher binding affinity than all other screened phytochemicals and the reference standard doxorubicin at both NF-κB and JAK1 targets, with stable complex formation confirmed over 200 ns of MD simulation. These findings position O. tenuiflorum, and rosmarinic acid specifically, as a promising, safer alternative to conventional chemotherapy. Future studies should focus on in vivo validation, bioavailability-enhancing nanoformulation strategies, and clinical evaluation to translate these findings toward adjunctive cancer therapy.
Oral carcinoma is a major global health concern and a leading cause of carcinoma-related mortality. This study evaluated a methanolic polyherbal extract for its phytochemical composition and biological efficacy, along with mechanistic insights via in silico network pharmacology. GC-MS and UPLC profiling confirmed diverse bioactive compounds, particularly polyphenols, with UV peaks at 272 nm. The extract showed strong antioxidant activity (IC₅₀ = 108 ± 0.17 µg/mL) and significant antimicrobial effects (inhibition zones: 6.00–21.33 mm). Cytotoxicity assays revealed anticancer activity against OECM-1 oral carcinoma cells (IC₅₀ = 18.86 µg/mL). The polyphenolic fraction suppressed pro-inflammatory cytokines (IL-6, IL-10, TNF-α, IL-1β, TGF-β) with IC₅₀ values of 3.02–6.15 µg/mL. Network pharmacology and molecular docking indicated multi-target interactions of key phytochemicals in pathways relevant to oral carcinoma progression. These findings suggest the polyherbal extract may be a complementary candidate in oral carcinoma management via antioxidant, anti-inflammatory, and antiproliferative effects.
E. Mary, L. Inbathamizh, V. Pandey et al.· Scientific Reports· 2 citations
Field cancerization in the upper respiratory tract (URT) heavily drives cancer recurrence. The present study evaluated Thai ethnobotanical ingredients from Kampramong’s anticancer remedies as alternative agents for URT cancer control. Thirty-one ethanolic extracts were screened for cytotoxicity against six URT malignant cell lines (HK1, KB, HONE-1, NPC38, NPC43, and HEp2) and two non-cancerous controls (NP460 and HaCaT) using the sulforhodamine B (SRB) assay. The selectivity index or IC50 ratio of normal cells/cancer cells was also determined for selective cytotoxicity of extracts and compounds. Anti-inflammatory activity was measured using the nitric oxide (NO) reduction assay. Antioxidant capacity was measured using the DPPH radical scavenging assay. Total flavonoid content (TFC) was measured due to the main risk reduction factor. Multivariate analyses (Hierarchical Cluster Analysis; HCA and Principal Component Analysis; PCA) were used for the relationship of flavonoids, NO inhibition drive to cytotoxicity. The best plant extracts and their cytotoxic compounds were also predicted to have their target molecular mechanisms by molecular docking. HCA identified Caesalpinia sappan, Coscinium fenestratum, and Tectona grandis as exhibiting potent cytotoxicity against all malignant cells, with C. sappan being the most potent. PCA revealed that flavonoid content and nitric oxide inhibition were the critical factors driving cytotoxicity (factor load 71.93%). Molecular docking of C. sappan compounds, brazilin and sappanchalcone, showed high binding energies with multiple core target proteins (MAPK1, MAPK3, SRC, AKT1, and GRB2), indicating a synergistic multi-compound, multi-target mechanism, representing a hypothesis for future mechanistic validation. Kampramong’s ethnobotanical remedies, particularly C. sappan, are promising candidates for URT malignancy treatment and field cancerization prevention, offering valuable data for future drug development.
Nanatphong Paje, A. Itharat, W. Chanvimalueng et al.· International Journal of Mol...· 0 citations
Lung cancer remains an aggressive and highly prevalent disease worldwide, causing an estimated 1.8 million deaths in 2022 and becoming a leading cause of cancer-related mortality. Resistance to current therapies necessitates novel approaches that target the tumour immune microenvironment (TIME), which is crucial for disease progression. Studies suggest that certain phytochemicals can enhance antitumour immunity by modulating the TIME. This systematic review aimed to elucidate and synthesise the mechanisms by which phytochemicals exert antitumour immunomodulatory effects in lung cancer and to assess their therapeutic potential and translational challenges. We comprehensively reviewed the literature from PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) until December 2025. Phytochemical mechanisms were analysed and classified based on their chemical structures and specific targets within the TIME. Phytochemicals effectively reprogrammed the immunosuppressive TIME using multi-target strategies. Key actions include the inhibition of immunosuppressive cells-such as myeloid-derived suppressor cells (MDSCs), Treg cells, and M2-polarised macrophages (e.g., via STAT3 downregulation by dihydroisotanshinone I)-activation of effector cells (e.g., NK cells, CD8+ T cells, and M1 macrophages), and the reversal of T helper cell drift (e.g., panaxan and aesculetin). This multipronged modulation offers superior efficacy by enhancing CD8+ T cell responses and overcoming functional exhaustion. This review validates the significant potential of phytochemicals as novel multi-target therapeutic agents for TIME-targeted therapy in lung cancer. Future research should prioritise addressing pharmacological challenges to accelerate rational clinical integration.
Feng Xiang, Liyue Lu, Fangfei Li et al.· Phytotherapy Research· 0 citations
Colorectal cancer (CRC) remains a major clinical challenge owing to its high mortality and limited therapeutic options, highlighting the urgent need for novel anticancer agents. Andrographolide (AGL), the principal bioactive compound isolated from the medicinal herb Andrographis paniculata, has demonstrated promising anticancer activity across multiple malignancies; however, its effects on CRC and the underlying molecular mechanisms remain poorly elucidated. Here, we systematically evaluated the anti-CRC potential of AGL using both in vitro and in vivo models. AGL significantly inhibited the proliferation of HT-29 and HCT-116 CRC cell lines in a dose- and time-dependent manner, induced G1-phase cell cycle arrest, suppressed cell migration, and promoted apoptosis and necrosis as determined by CCK-8 assays, flow cytometry, wound-healing assays, and YO-PRO-1/propidium iodide dual staining. Integrated transcriptomic and proteomic analyses of AGL-treated HT-29 cells revealed extensive gene and protein alterations enriched in pathways governing cell cycle control, apoptosis, and cancer-related signaling, and Western blotting confirmed the upregulation of pro-apoptotic proteins and downregulation of anti-apoptotic proteins. Importantly, AGL also significantly suppressed tumor growth in an HT-29 subcutaneous xenograft mouse model. Collectively, these findings demonstrate that AGL exerts potent anti-CRC activity primarily through the induction of G1-phase arrest and apoptosis, supporting its potential as a promising natural lead compound for the development of novel CRC therapeutics.
Haocheng Guan, Yongchao Li, Menglong Xu et al.· Current Issues in Molecular...· 0 citations
Ferulic acid, a natural phenolic phytotherapeutic, which is mainly found in plant cell walls, has attracted the attention of researchers for its multiple pharmacological properties, especially for its anti-tumor potential. As an efficient antioxidant, the compound counteracts oxidative stress and modulates key molecular pathways involved in carcinogenesis. Recent studies demonstrate that ferulic acid exerts antiproliferative, pro-apoptotic, and anti-metastatic effects in various tumor models, including colon, breast, liver, and lung cancers. Mechanistically, ferulic acid affects components of prosurvival-signaling pathways such as PI3K/Akt, MAPK, and NF-κB, and stimulates programmed cell death by diverse mechanisms, including apoptosis, autophagy and ferroptosis. Furthermore, its ability to sensitize cancer cells to chemotherapeutic drugs with low toxicity to normal cells underscores its therapeutic potential. Despite promising preclinical anti-tumor activity, low water solubility and bioavailability limit its clinical use. For this reason, several attempts, ranging from chemical derivatives to nanodevices, have been made to improve ferulic bioavailability and anti-tumor efficacy. This review highlights the most significant and recent strategies to ameliorate the anticancer ability of ferulic acid in the perspective of a clinical application.
T. Fiore, M. Giuliano, C. Pellerito et al.· International Journal of Mol...· 0 citations
Background: Worldwide, the incidence of melanoma and breast cancer, are increasing at an alarming rate. However, many existing anticancer drugs are losing efficacy due to increasing drug resistance and are often accompanied by unavoidable side effects. This growing challenge underscores the urgent need for novel and selective anticancer therapies. Traditional medicinal plants, such as kratom (Mitragyna speciosa), offer promising avenues for drug discovery in this regard. Methods: This work was performed to explore the in silico anticancer potential of compounds identified in M. speciosa leaf extract through Q-ToF LCMS analysis, alongside their physicochemical and pharmacokinetic parameters, to determine their suitability as lead candidates for anticancer drug development. A crude extract was prepared from kratom leaves using 100% methanol through ultrasound-assisted extraction yielding a 100% US extract with a recovery rate of 26.14%. The compounds were then screened in silicoagainst two cancer-related proteins (PDB IDs: 3OG7 and 3ERT) to evaluate their potential against melanoma and breast cancer. Results: The identified phenolic, flavonoid, and alkaloidal compounds showed potent binding interactions against the melanoma target. Finally, physicochemical and ADMET predictions revealed the potential of scopolin and 17-O-acetylajmaline as lead molecules for the development of new selective anticancer drugs to treat melanoma and breast cancer. Conclusion: The current study has identified promising lead compounds for the development of novel anticancer agents, offering valuable guidance for future research on kratom?based anticancer drug discovery.
Taslima Begum, Qamar Uddin Ahmed, A. H. Helal Uddin et al.· International Journal of All...· 0 citations
