Page 18 - EJMO-9-3

Eurasian Journal of
Medicine and Oncology Progress in the research of pathology and therapy in liver fibrosis

coated with SiO2 NPs, it exhibited greater bioavailability important role in anti-fibrotic clinical treatment. Ferulic
and minimal gastrointestinal reactions. 102 acid (FA), commonly found in natural products, is
Along the lines of PDGFR-β, chemokine receptor 4 widely utilized in the food and health industry. It exhibits
(CXCR4) is an important membrane surface receptor of antioxidant, anti-inflammatory, and anti-fibrotic effects in
activated HSCs, playing a vital role in the development of CCl4-induced liver injury through the protein-tyrosine
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chronic liver disease and liver fibrosis. 103-105 Both receptors phosphatases 1B-pAMPK signaling pathway. Both the
have been developed as targets for active targeting strategies active monomer methyl FA and the synthetic compound
of anti-fibrotic agents. Since PDGFR-β is co-expressed FA11 suppressed HSC activation and myofibroblast-
with the TNF-related apoptosis-inducing ligand (TRAIL) like transformation in LX-2 cells and CCl4-induced
receptor 2, polyethylene glycol-modified Z PDGFR β affibody mouse liver fibrosis, which may be attributed to the
exerted an exceptional anti-hepatocirrhosis effect inhibition of the TGF-β1/Smad and NOX4/ROS signaling
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compared to native TRAIL, by inducing HSC apoptosis and pathways. Zhao et al. reported the synergistic effect
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suppressing ECM accumulation. Another study found between astragaloside IV and FA in alleviating hepatic
that gold nanorods-PDGFR-β-mediated photothermal fibrosis induced by bile duct ligation (BDL). This effect
therapy reduced liver inflammation and hepatocyte injury was mediated by the activation of nuclear factor erythroid
in experimental models of liver fibrosis. Moreover, a 2-related factor 2 and the inactivation of glycogen
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novel nanocomplex composed of a polymeric CXCR4 synthase kinase-3β, along with the suppression of TGF-β1
antagonist, clodronate, and the siRNA of plasminogen expression and its downstream targets, Smad3 and Smad4.
activator inhibitor-1 represents a viable approach to The bioactive component isolated from Acanthus
treating liver fibrosis. This active HSC-targeted delivery ilicifolius, 4-hydroxy-2(3H)-benzoxazolone, significantly
system enhanced HSC uptake and exhibited expanded decreased the expressions of fibrotic markers (α-SMA and
anti-fibrotic activity through the synergistic regulation collagen) and ECM components by modulating multiple
of Kupffer cell apoptosis, ECM degradation, and HSC targets in the TGF-β1/Smads, nuclear factor-kappa B
inhibition. and extracellular signal-regulated kinase (ERK) signaling
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Liposome is naturally targeted to the liver and is mainly pathways. Both quercetin and isorhamnetin prevented
metabolized by the hepatic mononuclear phagocyte fibrosis by inhibiting the TGF-β1/Smads signaling
system. With the delivery of CXCR4-targeted liposomes, pathway, which reduced autophagy, ECM secretion,
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the accumulation of PFD and CXCR4 inhibitor in the and HSC activation after BDL- or CCl4-induced liver
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fibrotic liver increased, thus jointly inhibiting apoptotic injury. In addition to inducing autophagy, resveratrol
effects in HSCs through the significant downregulation of has been reported to have an anti-fibrotic effect in pre-
TGF-β1 expression. Even though the drug can aggregate clinical models by stimulating IL-4-like macrophage
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within the damaged liver, it has not significantly impacted polarization and regulating the microRNA-20a-mediated
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fibrosis progression. The overproduction of collagen in the tensin homolog/PI3K/AKT signaling pathway. Biejia
ECM greatly impedes drug delivery. A polymeric micelle ruangan tablets and fuzheng huayu (FZHY) capsules have
based on collagenase I has been developed to degrade been preliminarily confirmed to have antiviral effects
excessive ECM. A collagenase I and retinol polymeric in the treatment of HBV-related cirrhosis and have even
micelle loaded with the anti-fibrotic drug nilotinib was first shown regression of liver fibrosis when combined with
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synthesized, followed by the development of collagenase I entecavir therapy. When studying the mechanism
and Vitamin A polymeric micelle with siCol1α1, both of of FZHY in HSC inhibition, it was found that its main
which demonstrated favorable HSC-specific accumulation active component, Cordyceps sinensis mycelia (CS-PS),
and optimal anti-fibrotic activity in cellular experiments gypenosides, and amygdalin, can promote the degradation
and murine models. 110,111 Sorafenib, when co-delivered of ECM by regulating the MMPs/TIMPS ratio in a fibrotic
with collagenase I and glycyrrhetinic acid, presented rat model. In addition, FZHY exerted anti-hepatic fibrosis
excellent dual ability in reversing fibrotic liver and HSC effects by reducing hepatic apoptosis and inhibiting
internalization. The targeted NP delivery systems offer a TGF-β1/Smad signaling-mediated HSC activation. 125,126
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pioneering approach to liver fibrosis targeted therapy due to Thus, single-pathway or single-target blocking may not
their advantage of co-carrying multiple therapeutic agents. align with the actual mechanism of traditional Chinese
medicine due to its complex formulation.
3.5. Herbal medicine for liver fibrosis Through the TCM system pharmacology database and

In the treatment of liver fibrosis, valid herbal ingredients analysis platform, 14 components in Huangqi decoction
and traditional Chinese medicine (TCM) have played an were identified to be related to the downregulation of

Volume 9 Issue 3 (2025) 10 doi: 10.36922/ejmo.8125