Wild mountain ginseng, Panax ginseng Meyer, occupies a near-mythical status across Korea, China, and Japan, where it has been harvested for centuries as a medicinal herb and health food. Its value stems from ginsenosides, a family of triterpene saponins that constitute the plant’s primary pharmacological constituents. These compounds are conventionally divided into three structural groups: the protopanaxadiol type, which includes well-studied molecules such as Rb1, Rb2, Rb3, Rd, Rg3, and Rh2; the protopanaxatriol type, encompassing Re, Rf, Rg1, Rg2, and Rh1; and the oleanolic acid type, represented by Ro and related saponins. Decades of research have attributed a remarkable spectrum of biological activities to ginsenosides, including immune enhancement, antioxidant and antibacterial effects, antidiabetic and anti-inflammatory actions, anti-aging properties, and cardioprotective and neuroprotective benefits.

The problem, of course, is supply. A wild mountain ginseng root of this age is an extraordinarily rare resource, and demand for authentic, high-quality material far exceeds what nature can provide. The research team’s strategy was to sidestep the bottleneck entirely by generating adventitious roots, roots that arise from somatic tissue rather than from seed germination, from the 150-year-old specimen, designated 150y-Mg. These cultured roots were then scaled up in 1000-liter industrial bioreactors, where they grew in Murashige and Skoog medium supplemented with 5 percent sucrose by weight and 5 milligrams per liter of indole-3-butyric acid, a synthetic auxin that promotes root growth and ginsenoside accumulation.

The central question was whether the cultured roots could genuinely be considered the same plant. To answer it, the researchers turned to SNP genotyping, a technique that reads single-nucleotide variations scattered across the genome and produces a molecular fingerprint unique to each individual. Using a panel of 192 SNP markers, they compared the original mountain ginseng with two independently analyzed adventitious root samples. The result was unambiguous: 100 percent genotype concordance across the entire panel. Of the 192 loci, 184 were homozygous, meaning both copies of the gene carried the same variant, five were heterozygous, and three produced null calls that could not be scored. Calculated across the 189 callable non-null loci, the genetic fixation rate stood at 97.4 percent, a figure that reflects the high homozygosity typical of a long-lived, likely self-purging lineage rather than any discrepancy between the parent plant and its cultured offspring.

With genetic identity confirmed, the team shifted to the metabolome, the complete inventory of small molecules that defines what a plant actually produces. Liquid chromatography coupled with mass spectrometry, or LC–MS, revealed clear chemical differences among the analyzed materials. Within the sample set examined, malonyl ginsenoside Rb2/Rb3 was detected in the original 150-year-old mountain ginseng but not in cultivated Panax ginseng, whereas ginsenosides XVII and F2 appeared in the bioreactor-grown adventitious roots but were absent from cultivated ginseng under the same analytical conditions. The authors are careful to frame these observations as comparison-specific metabolite features rather than validated authentication markers, a distinction that matters for any future attempt to certify the origin of ginseng products in the marketplace.

That caution is scientifically warranted. A single comparison between one wild specimen and one cultivated reference cannot establish whether a particular metabolite is truly characteristic of age, habitat, or lineage. Environmental conditions, developmental stage, and analytical parameters can all shift the metabolic profile of ginseng tissue. What the LC–MS data do provide is a shortlist of candidate compounds, malonyl ginsenoside Rb2/Rb3, ginsenoside XVII, and ginsenoside F2, that now deserve systematic validation across broader and independent ginseng cohorts before they could ever serve as reliable markers of wild mountain provenance.

Complementing the LC–MS work, high-performance liquid chromatography, or HPLC, quantified the ginsenoside content of the adventitious roots and revealed distinct quantitative patterns that set them apart from conventional material. The relative proportions of individual saponins matter enormously for pharmacological activity, since different ginsenosides act on different molecular targets in the human body. A culture line that skews toward particular saponin classes could, with further optimization, become a standardized source of specific bioactive molecules, something that wild-harvested roots, with their inherent variability, can never guarantee.

The biomedical potential of the bioreactor-grown roots was explored through preliminary in vitro assays. These experiments provided early evidence of two activities of considerable commercial and clinical interest: anti-inflammatory effects and the ability to stimulate the proliferation of dermal papilla cells, the specialized fibroblasts at the base of hair follicles that regulate hair growth. The dermal papilla finding in particular hints at possible applications in cosmetics and hair-loss research, an area where ginseng-derived compounds have long attracted attention. The authors emphasize, however, that these are preliminary results, and the path from a cell-culture assay to a validated therapeutic or cosmetic ingredient involves extensive further testing.

What makes this study notable is not any single result but the complete pipeline it demonstrates. A rare, irreplaceable botanical resource was captured genetically, propagated indefinitely in sterile culture, scaled to industrial volumes, verified as a true genetic match, and profiled chemically and functionally, all without the plant ever leaving the laboratory. The 1000-liter bioreactor scale is the crucial detail here: it transforms what would otherwise be a botanical curiosity into a feasible production platform. Adventitious root culture of ginseng has been explored before, but anchoring the technology to a documented 150-year-old wild genotype, with SNP-level traceability, raises the standard for authenticity in an industry plagued by adulteration and mislabeling.

The researchers are candid about the limits of the current work. The metabolite features they observed are candidates, not conclusions, and the in vitro activities require confirmation in more rigorous models. Yet the foundation they have laid, complete genetic concordance, a reproducible culture system, and a defined chemical baseline, gives the field exactly what it needs to move forward: a stable reference material against which future wild and cultivated ginseng samples can be compared. If subsequent studies validate the candidate markers across independent cohorts, the combination of SNP fingerprinting and LC–MS profiling could become a powerful authentication toolkit. And if the anti-inflammatory and dermal papilla activities hold up, the roots of a plant that took 150 years to grow in the mountains may one day be produced by the ton, its ancient chemistry preserved in stainless steel tanks rather than in vanishing forest soil.

Subject of Research: Metabolomic profiling and bioreactor production of adventitious roots from a 150-year-old wild mountain ginseng

Article Title: Metabolomic profiling and biomedical potential of adventitious roots derived from a 150-year-old mountain ginseng

Article References: Lee, H.-S., Han, J.-E., Kwon, A.-R., Son, E.-J., Park, H., Kim, M.-O., Kim, Y. J., Lee, K. Y., Yang, T.-J., Murthy, H. N., Paek, K.-Y., & Park, S.-Y. (2026). Metabolomic profiling and biomedical potential of adventitious roots derived from a 150-year-old mountain ginseng. BMC Plant Biology. https://doi.org/10.1186/s12870-026-10136-1

Image Credits: AI Generated

DOI: 10.1186/s12870-026-10136-1

Keywords: Panax ginseng, mountain ginseng, ginsenosides, adventitious roots, metabolomics, LC-MS, SNP genotyping, plant biotechnology, bioreactor, anti-inflammatory, dermal papilla cells, BMC Plant Biology

Dermal papilla cells, or DPCs, sit at the base of the hair bulb and act as the command centre of the follicle. Richly supplied with blood vessels and nerves, they release a cocktail of paracrine signalling molecules, including vascular endothelial growth factor, fibroblast growth factors and Wnt ligands, that guide the proliferation and upward migration of surrounding follicular matrix cells. Those migrating cells then differentiate into the hair bulb and the inner and outer root sheaths, the protective sleeves that surround the growing hair shaft. DPCs effectively determine follicle size, the duration of the active growth phase known as anagen, and the overall rhythm of the hair cycle. When these cells malfunction, the consequences include follicle miniaturisation and atrophy, the hallmarks of conditions such as alopecia. Understanding what makes DPCs proliferate, and what holds them back, is therefore a central question in hair biology.

Androgens occupy a paradoxical position in this story. DHT, a potent metabolite of testosterone, promotes the growth of body hair in areas such as the beard and underarms, yet its excessive accumulation in genetically sensitive regions of the scalp drives androgenetic alopecia, the most common form of hair loss in humans. Previous studies have suggested that DHT may shift the balance between proliferation and apoptosis in DPCs by modulating pathways such as Wnt/β-catenin and TGF-β/Smad, but the precise mechanisms have remained elusive. The TGF-β superfamily comprises more than 30 ligands, including bone morphogenetic proteins, activins, inhibins and growth differentiation factors. In the canonical pathway, TGF-β ligands bind serine/threonine kinase receptors on the cell surface, triggering receptor-regulated Smads such as Smad2 and Smad3 to form complexes with the common mediator Smad4. These complexes enter the nucleus and regulate gene transcription, while inhibitory Smads such as Smad7 provide a built-in brake on the system.

The research team, working at Tarim University, chose their model with care. The Hetian sheep, an indigenous breed from the Hetian area of Xinjiang, is prized for high-quality wool and remarkable adaptation to extreme environments. Neonatal lambs, just three days old, were selected as donors because their dermal papilla cells show superior viability and proliferative potential, their low endogenous androgen levels minimise hormonal interference, and a uniform age group ensures biological consistency. Under institutional ethics approval, a small full-thickness skin sample was excised from the shaved dorsal skin of a healthy female lamb under local anaesthesia and strict aseptic conditions. The wound was treated with topical antibiotics and monitored daily until complete healing, reflecting the careful husbandry that underpins the entire cell culture enterprise.

Isolating the cells demanded considerable surgical precision at the microscopic scale. Skin specimens were minced into fragments and digested with collagenase type II at 37 degrees Celsius, after which intact hair follicles were separated by filtration and centrifugation. Using microdissection forceps and micro-spring scissors under a dissection microscope, researchers incised the narrowest region of the hair bulb, the dermal papilla neck, and gently detached the papilla with a glass capillary exploiting surface tension. Each isolated papilla was transferred to an individual well for primary culture. Within five days, polygonal cells migrated from the explants, forming growth halos that eventually covered half the well surface. By day twelve, the cultures had reached seventy to eighty percent confluency with a uniform, spindle-shaped morphology characteristic of healthy DPCs, and all nine replicate wells from the single donor were successfully established.

Identity verification was rigorous. Haematoxylin and eosin staining revealed cells with abundant nucleoli, while Giemsa staining highlighted the light-blue cytoplasm and central purplish-red nuclei. Chromosomal karyotype analysis confirmed 54 chromosomes per cell, comprising 26 pairs of autosomes and one pair of sex chromosomes, matching the standard sheep genome and proving the cells were genuinely of ovine origin. More decisively, double immunofluorescence staining demonstrated co-expression of CD133 and α-smooth muscle actin. CD133 is a surface marker highly expressed in human and murine DPCs but largely absent from other skin cell types, and recent hair follicle reconstitution assays have shown that CD133-high DPCs are the primary cellular drivers of new follicle formation. α-SMA, meanwhile, marks the contractile, myofibroblast-like properties that help DPCs maintain follicular structure. Together, these markers confirmed the cultures as authentic, hair-inductive dermal papilla cells.

With the model validated, the team turned to the central question: what does DHT do to these cells? Third-passage DPCs were treated with DHT concentrations spanning four orders of magnitude, from 1 to 1000 nanomolar, a range chosen to encompass physiologically relevant levels in androgen-responsive tissues and to extend into the supra-physiological realm to probe dose-dependent saturation. After 48 hours, the CCK-8 viability assay showed no significant differences across concentrations, but the more sensitive EdU assay, which directly measures DNA synthesis through flow cytometry, told a different story. Proliferation capacity rose steadily with increasing DHT concentration, peaking at 1000 nanomolar, where the difference from untreated controls reached statistical significance. The cells, in other words, were not merely surviving the hormone; they were dividing more vigorously in its presence.

The molecular explanation emerged from quantitative PCR analysis of eleven genes spanning the TGF-β ligand, receptor and Smad families. In cells treated with 1000 nanomolar DHT, expression of TGF-β1 and its receptor TGF-βRII was significantly downregulated, while TGF-β2 and TGF-β3 remained unchanged. Within the Smad family, DHT treatment reduced Smad2 and Smad6 expression, increased Smad5, and left Smad1, Smad3, Smad4 and Smad7 untouched. The pattern is mechanistically telling: Smad5 mediates BMP signalling, whereas Smad6 inhibits it, so the concurrent rise of Smad5 and fall of Smad6 suggests androgens may indirectly amplify BMP signalling, a pathway known to regulate follicle cycle timing, size and spacing. Meanwhile, the suppression of TGF-β1, a profibrotic cytokine that previous work has linked to reduced keratinocyte proliferation in co-culture, points to a release of the proliferative brake that TGF-β normally applies to the follicle microenvironment.

The authors are candid about the limits of the study. All experiments derived from a single biological donor, with replicates being technical rather than biological, and the pathway conclusions rest on gene expression data alone. Protein-level validation by Western blot, rescue experiments using exogenous TGF-β1 or pharmacological Smad inhibition, and in vivo or three-dimensional culture systems would all strengthen the causal chain between DHT, TGF-β/Smad suppression and DPC proliferation. The contrast with human scalp DPCs, where DHT has been reported to delay cell cycle progression without boosting proliferation, also underscores how tissue-specific and species-specific androgen responses can be; androgenetic alopecia is confined to genetically sensitive scalp regions and does not occur in normal skin. Even so, the establishment of the first Hetian sheep DPC culture is a genuine advance. It links androgen regulation to follicle development in a system directly relevant to wool fibre quality, potentially supporting higher wool yields and greater economic value for a distinctive livestock breed, while offering human hair researchers a comparative model whose skin biology mirrors our own more closely than rodents ever could. For a hormone best known for taking hair away, DHT has just revealed a surprising talent for building it, at least in sheep.

Subject of Research: Androgen regulation of dermal papilla cell proliferation via the TGF-β/Smad signalling pathway in Hetian sheep

Article Title: Dihydrotestosterone Promotes Hetian Sheep Dermal Papilla Cell Proliferation by Inhibiting the TGF‐β/Smad Signalling Pathway

Article References: Wang, Q., Liu, X., Feng, Z., Zhang, J., Li, C., Shi, R., & Li, S. (2026). Dihydrotestosterone Promotes Hetian Sheep Dermal Papilla Cell Proliferation by Inhibiting the TGF‐β/Smad Signalling Pathway. Veterinary Medicine and Science, 12(5), Article e71118. https://doi.org/10.1002/vms3.71118

Image Credits: AI Generated

DOI: 10.1002/vms3.71118

Keywords: dihydrotestosterone, dermal papilla cells, TGF-β/Smad pathway, Hetian sheep, hair follicle, androgenetic alopecia, wool quality, cell proliferation, Smad signalling, hair biology, Xinjiang livestock, primary cell culture