Key medicinal plants and phytochemicals with proven efficacy against HCC metastasis
S. No. | Scientific name | Common name | Active compound | Mechanism of action | Therapeutic potential | Reference |
---|---|---|---|---|---|---|
Apoptosis and cell cycle arrest | ||||||
1 | Ferula assa-foetida | Asafoetida-devil’s dung | Farnesiferol C | ↑ caspase activation results in increased apoptosis | Induction of apoptosis | [67] |
2 | Petroselinum crispum | Parsley | Apigenin | Induction of cell cycle arrest and apoptosis, inhibiting the PI3K/Akt signaling pathways by overexpression of miR-199a/b-5p | Cell cycle arrest, apoptosis | [55] |
Activates anti-angiogenic factor | ||||||
3 | Berberis vulgaris | Barberry | Berberine | Block the HIF-1α/VEGF axis, reduced expression of Id-1 by inactivation of p16INK4a/RB pathway | Anti-angiogenic | [68] |
4 | Solanum lycopersicum | Tomato | Lycopene | ↓ expression of HIF-1α, VEGF, CD31, MMP-2, and MMP-9 | Suppression of neovascularization | [69] |
Metabolic reprogram | ||||||
5 | Picrorhiza kurroa | Kutki | Picroside II | ↓ glycolytic enzyme expression activity | Metabolic reprogramming | [70] |
6 | Silybum marianum | Milk thistle | Silybin | Activating the AMPK-DR5 pathway inhibits intracellular ATP levels and glycolysis | ↓ ATP production and glycolysis | [71] |
Reduces tissue invasion | ||||||
7 | Arctium lappa | Greater burdock | Arctigenin | Wnt/β-catenin signaling, ↑ expression of E-cadherin, ↓ N-cadherin, and vimentin, prevent EMT | EMT suppression | [72] |
8 | Camptotheca acuminata | Happy tree | Camptothecin | ↓ expression of Nrf2, ↑ expression of E-cadherin, and ↓ N-cadherin | EMT inhibition | [73] |
9 | Curcuma longa | Turmeric | Curcumin | ↓ expression of MMPs-2/9, VEGF,inhibit the PI3K/Akt/mTOR/NF-κB signaling | EMT suppression, angiogenesis inhibition | [74] |
10 | Dioscorea zingiberensis | Zingiber yam | Diosgenin | Inhibit platelet activation, inhibit P2Y2 receptor activity, and ↑ E-cadherin expression | EMT inhibition and reducing metastatic potential | [75] |
11 | Glycyrrhiza inflata | Chinese licorice | Licochalcone A | Downregulation of the MKK4/JNK signaling pathway and NF-κB transcriptional activation | EMT inhibition | [76] |
12 | Glycine max | Soybean | Genistein | Inhibiting the EIF5A2/PI3K/Akt pathway, ↑ miR-1275, attenuate the EMT and stemness | EMT & stemness inhibition | [77] |
13 | Panax quinquefolius | Ginseng | Ginsenoside | Inhibit the HIF-1α and NF-κB signaling pathway, preventing EMT by ↓ vimentin and ↑ E-cadherin | EMT suppression | [78] |
14 | Plumbago zeylanica | Chitrak | Plumbagin | ↑ expression of E-cadherin and ↓ N-cadherin, vimentin, and snail, preventing EMT | EMT suppression | [79] |
15 | Rosmarinus officinalis | Rosemary | Rosmarinic acid | Inhibition of PI3K/Akt/mTOR signal pathway | Anti-invasion, anti-survival | [80] |
16 | Salvia miltiorrhiza | Danshen | Tanshinone IIA | ↓ expression of Rho GTPases regulates the cytoskeleton remodeling | EMT suppression | [81] |
17 | Scutellaria baicalensis | Chinese skullcap | Baicalein | ↓ expression of MMP-2, MMP-9, ↑ expression of TIMP-1 and 2 | Anti-invasion | [82] |
18 | Thymus vulgaris | Thyme | Carvacrol | Reduced the activity of argyrophilic nucleolar organizing regions, proliferating cell nuclear antigen, and MMPs-2/9 | Suppresses proliferation & metastasis | [83] |
19 | Withania somnifera | Ashwagandha | Withaferin A | ↓ expression of CD44, CD90, and EpCAM, inhibition of PI3K/Akt signaling pathway by ↑ miR-200c | EMT suppression | [84] |
Induces autophagy | ||||||
20 | Allium sativum L. | Garlic | Allicin | Induced autophagy | Cell survival regulation | [85] |
21 | Rheum palmatum | Turkish rhubarb | Emodin | Induced S and G2/M phase cell cycle arrest, induced autophagy, suppressed Wnt/β-catenin pathways | Inhibits proliferation and metastasis | [86] |
Activation of the immune system | ||||||
22 | Andrographis paniculata | King of bitters | Andrographolide | ↑ miR-22-3p expression level and ↓ HMGB1 and MMP-9 expression levels | Immunomodulation | [87] |
23 | Crocus sativus | Saffron crocus | Crocetin | ↑ expression of SHP-1, reduced activation STAT3, ↓ expression of MMP-9 | Inhibition of inflammation and invasion | [88] |
24 | Gentiana macrophylla | Qinjiao | Luteoloside | ↓ ROS level, ↓ expression of NLRP3, ↓ secretion of IL-1β | Anti-inflammatory response | [89] |
25 | Salvia miltiorrhiza | Danshen | Cryptotanshinone | ↓ IDO1 enzyme activity modulates immunoregulation | T cell modulation, immunoregulation | [90] |
26 | Terminalia bellirica | Bahera | Tannins | Modulating tumor immune microenvironment, restoration of CD8+ T cell infiltration and function | Reversal of immune suppression in the tumor microenvironment | [91] |
EMT: epithelial-mesenchymal transition; HCC: hepatocellular carcinoma; HIF-1α: hypoxia inducible factor-1α; Id-1: inhibitor of differentiation-1; IDO1: indoleamine 2,3-dioxygenase 1; MMP-2: matrix metalloproteinase-2; RB: retinoblastoma; VEGF: vascular endothelial growth factor
We also extend our utmost gratitude to Dr. Dinesh Kumar Meena, Research Scientist-II, St John’s Research Institute, Bangalore, for his invaluable insights and feedback on this manuscript.
MKN: Writing—original draft. DS and BV: Writing—review & editing.
The authors declare that there are no conflicts of interest.
This article is a review of previously published studies and does not involve human participants, animal subjects, or the collection of primary data; therefore, ethical approval was not required.
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This article is a review of previously published studies, and no new data were generated or analyzed in the course of this study. All data supporting the findings of this article are available in the cited references.
This work was supported by the JIPMER intramural research grant [JIP/Res/Intramural/Phase-4/2023-2024]. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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