---
title: "Natural products targeting HBx in HBV-related hepatocellular carcinoma: mechanisms and potential"
id: "pubmed-42693910"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42693910"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42693910/"
doi: "10.1080/13880209.2026.2724161"
published_at: "2026-09-04T12:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Natural products targeting HBx in HBV-related hepatocellular carcinoma: mechanisms and potential
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42693910
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42693910/)
- **DOI:** [10.1080/13880209.2026.2724161](https://doi.org/10.1080%2F13880209.2026.2724161)
- **Published At:** 2026-09-04T12:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Hepatocellular carcinoma (HCC) is frequently driven by chronic **HBV** infection; the viral X protein (**HBx**) is a multifunctional oncoprotein central to HBV persistence and hepatocarcinogenesis. - **HBx** disrupts transcriptional regulation, DNA repair, apoptosis, and immune responses, and thereby promotes malignant transformation and tumor progression. - This review surveyed the past decade of literature, including **in vitro**, **in vivo**, and clinical evidence, assessing natural products that directly or indirectly target **HBx** or **HBx**-associated pathways. - Some natural compounds suppress HBV replication by reducing **HBx** expression, enhancing **HBx** degradation, or limiting **HBx**-dependent **cccDNA** transcriptional activity. - Other bioactive natural products modulate downstream oncogenic processes linked to **HBx**, such as cell migration, invasion, liver fibrosis, metabolic reprogramming, and resistance to apoptosis. - The reviewed agents include plant-derived phytochemicals and non-plant natural compounds; specific compound names and doses were not provided in the abstract. - Evidence supporting activity comes from preclinical models and limited clinical data reported in the literature; the abstract does not list trial outcomes or detailed study metrics. - Authors conclude that **natural products** offer a promising multi-target therapeutic strategy for HBV-related HCC by intervening in **HBx**-driven oncogenic processes. - Key translational gaps identified include the need for mechanistic validation, standardization of bioactive compounds, and well-designed clinical trials to enable clinical application. - Overall, the review frames **HBx-targeted natural products** as potential adjunctive or alternative therapies for HBV-related HCC, while noting that further rigorous research is required.
## Clinical Analysis & Structured Key Points
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Epub 2026 Sep 4. # Natural products targeting hepatitis B virus X protein and HBx-associated pathways in HBV-related hepatocellular carcinoma: mechanisms and therapeutic potential [Thu Ngoc Anh Nguyen](https://pubmed.ncbi.nlm.nih.gov/?term=Nguyen+TNA&cauthor_id=42693910)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42693910/#full-view-affiliation-1 "Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand."), [Piyanoot Thongsri](https://pubmed.ncbi.nlm.nih.gov/?term=Thongsri+P&cauthor_id=42693910)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42693910/#full-view-affiliation-2 "Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand."), [Yongyut Pewkliang](https://pubmed.ncbi.nlm.nih.gov/?term=Pewkliang+Y&cauthor_id=42693910)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42693910/#full-view-affiliation-2 "Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand."), [Mullika Traidej Chomnawang](https://pubmed.ncbi.nlm.nih.gov/?term=Chomnawang+MT&cauthor_id=42693910)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42693910/#full-view-affiliation-3 "Department of Microbiology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42693910/#full-view-affiliation-4 "Antimicrobial Resistance Interdisciplinary Center \(AmRIC\), Faculty of Pharmacy, Mahidol University, Bangkok, Thailand."), [Krit Thirapanmethee](https://pubmed.ncbi.nlm.nih.gov/?term=Thirapanmethee+K&cauthor_id=42693910)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42693910/#full-view-affiliation-3 "Department of Microbiology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42693910/#full-view-affiliation-4 "Antimicrobial Resistance Interdisciplinary Center \(AmRIC\), Faculty of Pharmacy, Mahidol University, Bangkok, Thailand."), [Khanit Sa-Ngiamsuntorn](https://pubmed.ncbi.nlm.nih.gov/?term=Sa-Ngiamsuntorn+K&cauthor_id=42693910)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42693910/#full-view-affiliation-1 "Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42693910/#full-view-affiliation-4 "Antimicrobial Resistance Interdisciplinary Center \(AmRIC\), Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.") Affiliations Expand ### Affiliations * 1 Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand. * 2 Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. * 3 Department of Microbiology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand. * 4 Antimicrobial Resistance Interdisciplinary Center (AmRIC), Faculty of Pharmacy, Mahidol University, Bangkok, Thailand. * PMID: **42693910** * DOI: [ 10.1080/13880209.2026.2724161 ](https://doi.org/10.1080/13880209.2026.2724161) Item in Clipboard Review # Natural products targeting hepatitis B virus X protein and HBx-associated pathways in HBV-related hepatocellular carcinoma: mechanisms and therapeutic potential Thu Ngoc Anh Nguyen et al. Pharm Biol. 2026 Dec. Show details Display options Display options Format Abstract PubMed PMID Pharm Biol Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Pharm+Biol%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Pharm+Biol%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42693910/) . 2026 Dec;64(1):988-1016. doi: 10.1080/13880209.2026.2724161. Epub 2026 Sep 4. ### Authors [Thu Ngoc Anh Nguyen](https://pubmed.ncbi.nlm.nih.gov/?term=Nguyen+TNA&cauthor_id=42693910)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42693910/#short-view-affiliation-1 "Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand."), [Piyanoot Thongsri](https://pubmed.ncbi.nlm.nih.gov/?term=Thongsri+P&cauthor_id=42693910)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42693910/#short-view-affiliation-2 "Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand."), [Yongyut Pewkliang](https://pubmed.ncbi.nlm.nih.gov/?term=Pewkliang+Y&cauthor_id=42693910)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42693910/#short-view-affiliation-2 "Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand."), [Mullika Traidej Chomnawang](https://pubmed.ncbi.nlm.nih.gov/?term=Chomnawang+MT&cauthor_id=42693910)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42693910/#short-view-affiliation-3 "Department of Microbiology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42693910/#short-view-affiliation-4 "Antimicrobial Resistance Interdisciplinary Center \(AmRIC\), Faculty of Pharmacy, Mahidol University, Bangkok, Thailand."), [Krit Thirapanmethee](https://pubmed.ncbi.nlm.nih.gov/?term=Thirapanmethee+K&cauthor_id=42693910)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42693910/#short-view-affiliation-3 "Department of Microbiology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42693910/#short-view-affiliation-4 "Antimicrobial Resistance Interdisciplinary Center \(AmRIC\), Faculty of Pharmacy, Mahidol University, Bangkok, Thailand."), [Khanit Sa-Ngiamsuntorn](https://pubmed.ncbi.nlm.nih.gov/?term=Sa-Ngiamsuntorn+K&cauthor_id=42693910)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42693910/#short-view-affiliation-1 "Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42693910/#short-view-affiliation-4 "Antimicrobial Resistance Interdisciplinary Center \(AmRIC\), Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.") ### Affiliations * 1 Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand. * 2 Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. * 3 Department of Microbiology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand. * 4 Antimicrobial Resistance Interdisciplinary Center (AmRIC), Faculty of Pharmacy, Mahidol University, Bangkok, Thailand. * PMID: **42693910** * DOI: [ 10.1080/13880209.2026.2724161 ](https://doi.org/10.1080/13880209.2026.2724161) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Context:** Hepatocellular carcinoma (HCC), largely driven by chronic hepatitis B virus (HBV) infection, remains a major global health challenge with limited curative options in advanced stages. The hepatitis B virus X protein (HBx) is a multifunctional viral oncoprotein that plays a central role in HBV persistence and hepatocarcinogenesis by disrupting transcriptional regulation, DNA repair, apoptosis, and immune responses. **Objective:** This review aims to evaluate the role of HBx in HBV‑related HCC progression and to examine the therapeutic potential of natural products that directly target HBx and indirectly modulate HBx‑driven antiviral and oncogenic pathways. **Methods:** A comprehensive literature analysis was conducted focusing on studies published over the past decade, including _in vitro_ , _in vivo_ , and clinical evidence addressing HBx-mediated mechanisms and the pharmacological effects of bioactive natural products, including plant‑derived phytochemicals and non‑plant natural compounds. **Results:** Accumulating evidence indicates that some natural products suppress HBV replication by reducing HBx expression, promoting HBx degradation, or limiting HBx‑dependent cccDNA transcription, whereas others primarily influence biological pathways associated with HBx‑driven hepatocarcinogenesis, including migration, invasion, fibrosis, metabolic reprogramming, and apoptosis resistance. **Conclusion:** Natural products represent a promising multi-target therapeutic strategy for HBV-related HCC by intervening in HBx-driven oncogenic processes. Future studies should focus on mechanistic validation, standardization of bioactive compounds, and well-designed clinical trials to support their translational application as adjunctive or alternative therapies. **Keywords:** HBx protein; HBx‑targeted therapy; Hepatitis B virus; bioactive compounds; cccDNA; hepatocellular carcinoma; natural products. 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