Home›Drug Pipeline› Polyherbal Unani Formulation Targets TGF-beta/Smad, NF-kappaB, and PI3K/Akt Pathways in Fibrosis and Cancer
Polyherbal Unani Formulation Targets TGF-beta/Smad, NF-kappaB, and PI3K/Akt Pathways in Fibrosis and CancerPolyherbal Unani Formulation shows potential to treat cancer and fibrosis
Frontiers in MedicinePublished September 13, 2026DOI ↗Editorial oversight: Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development
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Key Takeaway
Interpret PUF preclinical mechanism data cautiously; clinical validation is lacking.
This systematic review synthesizes preclinical evidence on a polyherbal Unani formulation (PUF) containing chebulinic acid, picrosides, flavonoids, and phenolic derivatives for fibrosis-related diseases and aggressive cancers with fibrosis. The review focuses on molecular mechanisms rather than clinical outcomes.
The authors report that preclinical evaluation established effectiveness in modulating key molecular targets, including oxidative stress, pro-fibrotic signalling pathways (TGF-beta/Smad, NF-kappaB, PI3K/Akt), epithelial-mesenchymal transition (EMT), and fibroblast-to-myofibroblast plasticity. No effect sizes, p-values, or confidence intervals were reported.
Safety data, including adverse events, serious adverse events, discontinuations, and tolerability, were not reported. The review notes that phytochemical standardisation, bioavailability, and clinical validation remain significant challenges for the formulation.
Funding or conflicts of interest were not reported. The potential integrative therapeutic approach for fibrosis-related diseases and aggressive cancers with fibrosis is described, but clinical validation is lacking. Practice relevance remains uncertain given the absence of clinical outcome data.
How this fits prior evidence
This systematic review of preclinical mechanisms contrasts with prior coverage of clinical cancer interventions, such as intraoperative dexmedetomidine showing no significant impact on cancer survival outcomes, and the Hamburg Life After Cancer Program protocol focused on quality of life. It also differs from the mapping review of quercetin immunity research, which identified 12 thematic clusters without clinical efficacy data. Like the review of FDA-approved AI solutions for cancer histopathology, which found only 4 approved solutions, this review highlights an emerging area where clinical translation is limited. It addresses a gap in synthesized evidence for polyherbal formulations in fibrosis and cancer, but remains preclinical.
Living with conditions like cancer or fibrosis often involves dealing with intense internal scarring. This process, known as fibrosis, makes tissues stiff and harder for the body to function. Researchers are looking into a traditional herbal blend called Polyherbal Unani Formulation (PUF) to see if it can slow these processes down.
In early laboratory tests, this herbal mix showed it could target specific pathways that cause scarring. It worked by reducing oxidative stress and blocking certain signals that tell cells to turn into scar-forming cells. Specifically, it targeted pathways like TGF-beta/Smad and NF-kappaB, which are often involved in aggressive cancer growth and tissue hardening.
While these early results are promising for creating new treatments, there are still big hurdles to clear. The researchers noted that the ingredients need better standardization and the body's ability to absorb the medicine is not yet fully known. Because these are early findings, more clinical testing is needed to see how it works in people.
What this means for you:
A traditional herbal blend shows promise in lab tests for slowing down tissue scarring and cancer growth.
Common questions
What is the Polyherbal Unani Formulation?
It is a herbal blend containing chebulinic acid, picrosides, flavonoids, and phenolic derivatives. These components were tested in laboratory settings to see if they could block the signals that cause tissue scarring and help manage conditions like cancer and fibrosis.
How does this herbal blend work against fibrosis?
The mixture works by reducing oxidative stress and blocking specific pathways like TGF-beta/Smad and NF-kappaB. It also helps stop the process where cells change into scar-forming cells, which is a key part of how fibrosis develops in the body.
Is this treatment ready for patients to use?
Not yet. While the early laboratory tests are promising, the researchers noted that the medicine still faces challenges with bioavailability and standardization. More clinical validation is needed before it can be used as a standard treatment for patients.
Fibrosis is a pathological condition characterised by excessive deposition of the extracellular matrix (ECM) and persistent activation of myofibroblasts, and is associated with many chronic diseases. The association between fibrosis and cancer is increasingly recognised, where fibrosis contributes to the progression of cancer by increasing metastatic potential and resistance to therapy, thereby leading to poor clinical outcomes. A novel Polyherbal Unani Formulation (PUF), based on the Unani system of medicine, possesses a distinct phytochemical constitution with wide-spectrum therapeutic properties. Phytochemicals such as chebulinic acid, picrosides, flavonoids, and phenolic derivatives are reported to exert multi-targeted effects by attenuating oxidative stress, suppressing pro-fibrotic signalling pathways (TGF-β/Smad, NF-κB, PI3K/Akt), inhibiting epithelial-mesenchymal transition (EMT), and restoring fibroblast-to-myofibroblast plasticity. These individual compounds were systematically evaluated preclinically, establishing their effectiveness in modulating key molecular targets. Challenges such as phytochemical standardisation, bioavailability, and clinical validation remain significant for this distinct drug formulation, thereby improving its translational value. This review article considers PUF as a potential integrative therapeutic approach for fibrosis-related diseases and for aggressive cancers with fibrosis. In summary, we expect this PUF to target both tumour cells and the fibrotic tumour micro-environment, thereby integrating ethnopharmacological knowledge with molecular rationality.
