From:  The role of medicinal plants in the management of hepatocellular carcinoma and its metastasis

 Key medicinal plants and phytochemicals with proven efficacy against HCC metastasis

S. No.Scientific nameCommon nameActive compoundMechanism of actionTherapeutic potentialReference
Apoptosis and cell cycle arrest
1Ferula assa-foetidaAsafoetida-devil’s dungFarnesiferol C↑ caspase activation results in increased apoptosisInduction of apoptosis[67]
2Petroselinum crispumParsleyApigeninInduction of cell cycle arrest and apoptosis, inhibiting the PI3K/Akt signaling pathways by overexpression of miR-199a/b-5pCell cycle arrest, apoptosis[55]
Activates anti-angiogenic factor
3Berberis vulgarisBarberryBerberineBlock the HIF-1α/VEGF axis, reduced expression of Id-1 by inactivation of p16INK4a/RB pathwayAnti-angiogenic[68]
4Solanum lycopersicumTomatoLycopene↓ expression of HIF-1α, VEGF, CD31, MMP-2, and MMP-9Suppression of neovascularization[69]
Metabolic reprogram
5Picrorhiza kurroaKutkiPicroside II↓ glycolytic enzyme expression activityMetabolic reprogramming[70]
6Silybum marianumMilk thistleSilybinActivating the AMPK-DR5 pathway inhibits intracellular ATP levels and glycolysis↓ ATP production and glycolysis[71]
Reduces tissue invasion
7Arctium lappaGreater burdockArctigeninWnt/β-catenin signaling, ↑ expression of E-cadherin, ↓ N-cadherin, and vimentin, prevent EMTEMT suppression[72]
8Camptotheca acuminataHappy treeCamptothecin↓ expression of Nrf2, ↑ expression of E-cadherin, and ↓ N-cadherinEMT inhibition[73]
9Curcuma longaTurmericCurcumin↓ expression of MMPs-2/9, VEGF,
inhibit the PI3K/Akt/mTOR/NF-κB signaling
EMT suppression, angiogenesis inhibition[74]
10Dioscorea zingiberensisZingiber yamDiosgeninInhibit platelet activation, inhibit P2Y2 receptor activity, and ↑ E-cadherin expressionEMT inhibition and reducing metastatic potential[75]
11Glycyrrhiza inflataChinese licoriceLicochalcone ADownregulation of the MKK4/JNK signaling pathway and NF-κB transcriptional activationEMT inhibition[76]
12Glycine maxSoybeanGenisteinInhibiting the EIF5A2/PI3K/Akt pathway, ↑ miR-1275, attenuate the EMT and stemnessEMT & stemness inhibition[77]
13Panax quinquefoliusGinsengGinsenosideInhibit the HIF-1α and NF-κB signaling pathway, preventing EMT by ↓ vimentin and ↑ E-cadherinEMT suppression[78]
14Plumbago zeylanicaChitrakPlumbagin↑ expression of E-cadherin and ↓ N-cadherin, vimentin, and snail, preventing EMTEMT suppression[79]
15Rosmarinus officinalisRosemaryRosmarinic acidInhibition of PI3K/Akt/mTOR signal pathwayAnti-invasion, anti-survival[80]
16Salvia miltiorrhizaDanshenTanshinone IIA↓ expression of Rho GTPases regulates the cytoskeleton remodelingEMT suppression[81]
17Scutellaria baicalensisChinese skullcapBaicalein↓ expression of MMP-2, MMP-9, ↑ expression of TIMP-1 and 2Anti-invasion[82]
18Thymus vulgarisThymeCarvacrolReduced the activity of argyrophilic nucleolar organizing regions, proliferating cell nuclear antigen, and MMPs-2/9Suppresses proliferation & metastasis[83]
19Withania somniferaAshwagandhaWithaferin A↓ expression of CD44, CD90, and EpCAM, inhibition of PI3K/Akt signaling pathway by ↑ miR-200cEMT suppression[84]
Induces autophagy
20Allium sativum L.GarlicAllicinInduced autophagyCell survival regulation[85]
21Rheum palmatumTurkish rhubarbEmodinInduced S and G2/M phase cell cycle arrest, induced autophagy, suppressed Wnt/β-catenin pathwaysInhibits proliferation and metastasis[86]
Activation of the immune system
22Andrographis paniculataKing of bittersAndrographolide↑ miR-22-3p expression level and ↓ HMGB1 and MMP-9 expression levelsImmunomodulation[87]
23Crocus sativusSaffron crocusCrocetin↑ expression of SHP-1, reduced activation STAT3, ↓ expression of MMP-9Inhibition of inflammation and invasion[88]
24Gentiana macrophyllaQinjiaoLuteoloside↓ ROS level, ↓ expression of NLRP3, ↓ secretion of IL-1βAnti-inflammatory response[89]
25Salvia miltiorrhizaDanshenCryptotanshinone↓ IDO1 enzyme activity modulates immunoregulationT cell modulation, immunoregulation[90]
26Terminalia belliricaBaheraTanninsModulating tumor immune microenvironment, restoration of CD8+ T cell infiltration and functionReversal 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