The research, carried out by an international team working across institutes in Iran and Germany, including the Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) in Gatersleben and Shiraz University, took on one of the most persistent challenges in medicinal plant science: connecting visible chemical traits to the underlying genetic code. The team genotyped 175 accessions and populations spanning the genus Glycyrrhiza using genotyping-by-sequencing, a technique that slashes the cost of genome-wide profiling by sequencing only the most informative slices of DNA. From this effort they assembled a catalogue of 38,393 high-quality single-nucleotide polymorphisms, or SNPs—individual letter changes scattered across the genome that serve as signposts for comparative genetics.

The first major finding concerns how licorice species relate to one another. Genetic structure analysis showed that G. glabra, the species that produces the celebrated medicinal root, is mostly distinct from its relatives in the genus. This genetic separation matters for conservationists and breeders alike, because it indicates that G. glabra carries a unique reservoir of variation that cannot simply be recovered from closely related species. Within G. glabra itself, the analysis identified a coherent group of 66 plants drawn from 33 Iranian origins, showing moderate genetic differentiation from other accessions. Iran, with its long tradition of licorice harvesting and its position at the heart of the plant’s natural range, appears to shelter a genetically recognizable and potentially valuable portion of the species’ diversity.

With the population structure established, the researchers turned to the central question: which genomic regions control the accumulation of the plant’s bioactive metabolites? They focused on three medically important traits and deployed genome-wide association mapping, a statistical approach that scans thousands of SNPs for correlations with measured phenotypes across many individuals. The results were striking. Twenty highly significant SNP associations emerged in total. Fifteen of them were linked to glabridin in the cork layer of the root, and three of those were also associated with glabridin in the fleshy texture of the root. Five additional SNPs were associated with liquiritigenin in the cork layer.

Those two compounds deserve attention on their own terms. Glabridin is the signature flavonoid of licorice, prized for anti-inflammatory, skin-brightening, antioxidant, and antimicrobial properties, and it is a staple ingredient in cosmetic and pharmaceutical pipelines worldwide. Liquiritigenin is another flavonoid with documented pharmacological activity and a key position in the flavonoid biosynthetic pathway of the plant. Intriguingly, both molecules are described as players in biotic and abiotic stress responses, meaning the plant likely deploys them as chemical shields against pathogens and harsh environmental conditions. The new genetic associations suggest that the very loci breeders might select for higher medicinal content are also tied to how robustly the plant defends itself—a potentially powerful linkage for developing resilient, potent cultivars simultaneously.

Because association mapping identifies genomic neighborhoods rather than single causal genes, the team followed up by searching for candidate genes near the significant SNPs. The list they assembled reads like a who’s who of plant secondary metabolism regulation. Among them stands MYB6, a transcription factor known to activate flavonoid-biosynthetic genes, making it an obvious lever for engineering or selecting plants that produce more glabridin. Another candidate, an OCTOPUS-like gene, plays a role in the differentiation of primary root protophloem and overall root architecture—a fascinating connection, since the metabolites of interest accumulate in specific root tissues, and the internal anatomy of the root may determine where and how much compound is stored.

The candidate list also includes WRKY transcription factors, a large family of regulators that modulate phenylpropanoid, alkaloid, and terpene pathways. WRKY genes are central switches in plant defense signaling, and their presence near the associated loci reinforces the idea that licorice’s medicinal chemistry is deeply entangled with its stress biology. A fourth candidate, aminodeoxychorismate synthase, adds a further layer of metabolic intrigue, hinting that primary metabolism feeds into the specialized chemistry of the root in ways that association mapping can now expose. Together, these genes sketch a plausible molecular chain running from environmental sensing through transcriptional control to the final accumulation of flavonoids in root tissues.

Methodologically, the study demonstrates how modern genomic tools can transform a traditionally understudied medicinal crop. Genotyping-by-sequencing allowed the team to characterize genetic structure and run association mapping in a genus for which genomic resources have been scarce, without requiring a fully assembled reference genome. The combination of population structure analysis, principal component approaches, and mixed linear models for association testing reflects the current best practice for avoiding false positives caused by population stratification—a notorious pitfall when working with geographically structured plant collections such as this one.

The practical implications reach well beyond the laboratory. Wild and landrace licorice populations face pressure from overharvesting and habitat loss, and cultivated varieties often lag behind wild roots in medicinal compound content. By identifying SNP markers linked to glabridin and liquiritigenin accumulation, the study gives breeders molecular tools to screen seedlings for high-value chemistry long before the roots mature—a process that would otherwise take years of cultivation and costly chemical assays. Marker-assisted selection built on these loci could accelerate the development of improved Glycyrrhiza varieties with enhanced medicinal properties, while the genetic structure data can guide the conservation of the species’ most distinctive populations, including the Iranian group highlighted by the analysis.

For a genus that has served human medicine since antiquity, licorice has been surprisingly slow to enter the genomic era. This study changes that, delivering both a comprehensive picture of genetic diversity across Glycyrrhiza species and a concrete set of molecular handles on the chemistry that makes the root valuable. As demand for plant-derived therapeutics grows and climate change tightens the screws on medicinal crop production, the ability to read—and eventually write—the genetic instructions behind licorice’s chemical defenses may prove to be one of the more consequential developments in medicinal plant genomics of the coming decade.

Subject of Research: Genetic structure and SNP associations with secondary metabolites in Glycyrrhiza species and G. glabra

Article Title: Genetic structure analysis of Glycyrrhiza species and identification of SNP-loci associated with secondary metabolites in G. glabra

Article References: Moghadam, A., Karami, A., Kellert, B., Haghi, R., Esmaeili, H., Himmelbach, A., & Otto, L.-G. (2026). Genetic structure analysis of Glycyrrhiza species and identification of SNP-loci associated with secondary metabolites in G. glabra. BMC Genomics, 27(1), Article 767. https://doi.org/10.1186/s12864-026-13361-y

Image Credits: AI Generated

DOI: 10.1186/s12864-026-13361-y

Keywords: licorice, Glycyrrhiza glabra, SNP, genotyping-by-sequencing, GWAS, glabridin, liquiritigenin, flavonoid biosynthesis, genetic diversity, medicinal plants, MYB6, plant breeding

Glycyrrhizin, also known as glycyrrhizinic or glycyrrhizic acid, accumulates in the roots and rhizomes of Glycyrrhiza glabra, the classic liquorice plant, as well as related species such as G. uralensis and G. inflata. On hydrolysis it yields 18β-glycyrrhetinic acid, also called glycyrrhetic acid or enoxolone, which is itself biologically active. The molecule’s commercial and clinical portfolio is remarkably broad. Its monoammonium salts serve as high-intensity sweeteners, and it is the chemical precursor for carbenoxolone, a hemisuccinyl ester derivative with mineralocorticoid activity that is marketed as an antiulcer drug. The review emphasizes that pharmacological studies have documented antiviral activity against hepatitis B and influenza A/H1N1 viruses, anti-inflammatory effects demonstrated through albumin denaturation assays and in ulcerative colitis, anticancer activity in colorectal cancer cell lines SW620 and HT29, and growth suppression of A549 lung adenocarcinoma cells through inhibition of thromboxane synthase.

Clinical evidence further strengthens the case for scaling up production. Glycyrrhizin has been tested alone and in combination therapies for chronic hepatitis C, including in interferon-resistant patients, where injection therapy has been associated with reduced hepatocellular carcinogenesis. A randomized placebo-controlled trial explored glycyrrhizic acid as an adjunctive treatment for depression through anti-inflammatory mechanisms. Against this backdrop of expanding medical relevance, the natural content of glycyrrhizin in even the richest licorice roots remains very low, and wild plants typically need three to four years of growth before harvest, creating a pressing supply problem that the review’s authors set out to address systematically.

Understanding the biosynthetic pathway is the foundation of every enhancement strategy. Glycyrrhetinic acid is an oleanane-type triterpenoid built through the mevalonate pathway from repeated units of isopentenyl pyrophosphate and dimethylallyl pyrophosphate. The pivotal first committed step is the cyclization of 2,3-oxidosqualene into β-amyrin, catalyzed by β-amyrin synthase. From there, sequential oxidation reactions driven mainly by the cytochrome P450 enzymes CYP88D6 and CYP72A154 generate a series of intermediates that culminate in glycyrrhetinic acid. The glycoside is then assembled by glycosyltransferases: UDP-glucose dehydrogenase converts UDP-glucose to UDP-glucuronic acid, and the enzyme UGT73P12 transfers a glucuronic acid moiety to the third carbon of glycyrrhetinic acid, forming glycyrrhetic acid 3-O-mono-β-D-glucuronide, or GAMG. A second glucuronosylation event on GAMG completes glycyrrhizin, with UDP-glucose pyrophosphorylase, known as UGP1, regenerating the UDP-glucose donor.

The most extensively explored strategy for boosting glycyrrhizin is elicitation, in which cultured plant tissues are deliberately stressed with biotic or abiotic agents to switch on secondary metabolism. The earliest in vitro attempt, by Shabani and colleagues in 2009, treated Glycyrrhiza glabra cultures with methyl jasmonate and salicylic acid at concentrations from 0.01 to 2.0 millimolar. Glycyrrhizin peaked at 0.1 millimolar methyl jasmonate after eight hours, while salicylic acid raised content up to 1 millimolar but depressed it at 2 millimolar, an early demonstration that elicitor dose and timing follow narrow windows of benefit. In 2010, Karwasara and colleagues extended the approach to cell cultures of Abrus precatorius, a related legume, finding that culture filtrate of Aspergillus niger at 7.5 percent and dried cell powder of Rhizopus stolonifer at 0.5 percent, together with yeast extract and 50 micromolar ascorbic acid, maximized both biomass and glycyrrhizin accumulation.

Subsequent work has diversified the elicitor toolkit considerably. Srivastava and colleagues subjected Agrobacterium rhizogenes-induced hairy roots of G. glabra to drought-mimicking PEG 6000, the heavy metal cadmium chloride, and the biotic elicitors cellulase and mannan. Polyethylene glycol at 1 percent produced the highest glycyrrhizin after 24 hours, cellulase at 200 micrograms per milliliter progressively raised content over seven days, and remarkably the lowest mannan dose of 10 milligrams per liter yielded the peak concentration of 3.3089 micrograms per milligram after ten days. In Taverniera cuneifolia root cultures, Awad and colleagues screened six fungal and five bacterial elicitors and found that Rhizobium leguminosarum drove glycyrrhizic acid to 6 milligrams per gram, while methyl jasmonate at 100 micromolar delivered a 2.5-fold increase. Jaiswal and colleagues, meanwhile, showed that adenine sulphate outperformed biotin, salicylic acid and polyamines in G. glabra callus, reaching 35.44 micrograms per gram, likely because sulphate assimilation supports amino acid and metabolite synthesis.

Microbial partners and physical stimuli have added further dimensions. Li and colleagues raised glycyrrhizin in adventitious roots of G. uralensis with low-dose salicylic acid, optimal sucrose at 4 percent and one-strength MS salts, and later showed that Aspergillus niger treatments in 5-liter balloon-type bubble bioreactors increased glycyrrhizin up to 200 milligrams per liter of elicitor, though higher doses reversed the effect. Xie and colleagues reported that the plant growth-promoting bacterium Bacillus pumilus, inoculated into drought-stressed G. uralensis plants, reduced antinutritional factors, improved protein digestibility and boosted antioxidants, cumulatively enhancing glycyrrhizin biosynthesis. In G. inflata hairy roots, methyl jasmonate at 100 micromolar produced 5.7 times more glycyrrhizin than controls after five days, whereas chitosan proved ineffective. Allahdou and colleagues found cellulase from Aspergillus niger at 200 micrograms per milliliter optimal for both glycyrrhizin and glycyrrhetinic acid in G. glabra hairy roots, and Afsharzadeh and colleagues combined hairy root transformation with red and blue LED light, recording antioxidant capacity gains over 55 days of exposure. Most strikingly, Yamamoto and colleagues documented overwhelming glycyrrhizin induction through symbiosis with the nitrogen-fixing rhizobium Mesorhizobium sp. J8, which elevated chlorophyll, nitrogenase activity and the expression of genes for glycyrrhizin and jasmonic acid synthesis.

Beyond elicitation, the review highlights genome editing as a fundamentally different lever. Chiyo and colleagues in 2023 used CRISPR/Cas9 in G. uralensis hairy roots to knock out the genes CYP93E3 and CYP72A566, which divert flux toward soyasaponins, along with CYP716A179 for oleanolic acid and LUS1 for betulinic acid. By eliminating these competing branches of β-amyrin metabolism, more precursor was channeled toward glycyrrhetinic acid and ultimately glycyrrhizin. When pathway blocking was paired with overexpression of CYP88D6, the oxidation step toward glycyrrhetinic acid, glycyrrhizin production rose again. Although the absolute gains were modest, the authors note that the results were achieved within a single month of culture, a dramatic contrast to the three to four years required by wild licorice, illustrating how pathway rationalization could compress production timelines.

The third pillar is heterologous biosynthesis in microbes, which began when Zhu and colleagues engineered 11-oxo-β-amyrin and glycyrrhetinic acid synthesis into Saccharomyces cerevisiae in 2017. In 2019, Wang and colleagues integrated codon-optimized CYP88D6 and CYP72A154, together with β-amyrin synthase and an Arabidopsis thaliana NADPH-cytochrome P450 reductase, into the yeast chromosome, producing a strain that yielded 2.5 milligrams per liter of β-amyrin and 14 micrograms per liter of glycyrrhetinic acid. Introducing a cytochrome b5 from G. uralensis multiplied glycyrrhetinic acid output eightfold, and combining both strategies achieved a 40-fold improvement to 0.5 milligrams per liter in batch fermentation, extended to a 630-fold improvement reaching 8.78 milligrams per liter in fed-batch mode. The review cautions that plant P450 enzymes often show reduced catalytic activity in yeast and can interact poorly with reductases, generating reactive oxygen species that impair cell growth and product yield.

Taken together, the review paints a picture of a field converging on integrated solutions. Every elicitation regime, whether chemical, microbial or physical, works by provoking the plant’s in vitro defense machinery, and every approach shows a concentration ceiling beyond which toxicity erases the gains. The glycyrrhizin pathway is multifaceted and compartmentalized, limiting metabolite flux, and many of its genes and regulators remain unknown, while gene editing can sometimes merely redirect accumulation into other unintended metabolites. Even so, the authors conclude that the enhancements already demonstrated carry genuine commercial value, both for glycyrrhizin and its carbenoxolone derivative, and that the same elicitation, editing and engineering playbook is readily transferable to other plant secondary metabolites, positioning licorice biotechnology as a template for the sustainable production of high-value natural products worldwide.

Subject of Research: Biotechnological strategies for enhancing glycyrrhizin biosynthesis in licorice and engineered microbes

Article Title: An overview of strategies used for increasing Glycyrrhizin biosynthesis

Article References: Patil, S. P., Patil, R. R., Kore, S. D., & Raut, M. K. (2026). An overview of strategies used for increasing Glycyrrhizin biosynthesis. Discover Industrial Chemistry and Materials, 1(1), Article 7. https://doi.org/10.1007/s44508-026-00008-9

Image Credits: AI Generated

DOI: 10.1007/s44508-026-00008-9

Keywords: glycyrrhizin, licorice, Glycyrrhiza glabra, elicitation, CRISPR, Saccharomyces cerevisiae, secondary metabolites, metabolic engineering, hairy root cultures, triterpenoid saponin, glycyrrhetinic acid, plant tissue culture

The research team, led by Ruizhi Fan, Zeyuan Li, Meihua Liang, Chunyan Zhao, Xueli Wang and corresponding author Zhibin Zhang of Shanxi University of Traditional Chinese Medicine, systematically searched PubMed, Embase, the Cochrane Library and Web of Science for randomized controlled trials testing plant-based interventions in patients with allergic rhinitis. Their final dataset comprised 27 randomized controlled trials encompassing 1,681 participants, with studies published up to March 2025. Methodological quality was assessed with the Cochrane Risk of Bias Tool, and the statistical analysis, performed in Stata 15.4, employed a Bayesian network meta-analysis framework using Markov Chain Monte Carlo methods to allow both direct and indirect comparisons among interventions.

What distinguishes a network meta-analysis from a conventional pairwise meta-analysis is its ability to rank treatments even when they have never been compared head-to-head in a single trial. The team quantified each intervention’s performance using SUCRA values—the surface under the cumulative ranking curve—where a value approaching 100 percent signals the highest probability of being the most effective option in the network. The interventions ranged from well-known supplements such as spirulina and Pycnogenol to more specialized botanicals including Benifuuki green tea, broccoli sprout extract, fermented red ginseng, Perilla frutescens extract, Nigella sativa oil, stinging nettle root extract and Petasites hybridus leaf extract (Ze 339).

The rankings that emerged are strikingly specific to the outcome measured. For Total Nasal Symptom Scores, the primary clinical metric combining congestion, rhinorrhea, sneezing and itching, tomato extract rose to the top with a SUCRA value of 78.0 percent, suggesting it may offer the most consistent relief of core nasal symptoms. Glycyrrhiza glabra, commonly known as licorice, led the network for reducing Sino-Nasal Outcome Test-22 scores—a validated patient-reported instrument capturing nasal, sleep and emotional domains of sinonasal disease—with a SUCRA of 92.6 percent.

Spirulina, the blue-green cyanobacterium widely consumed as a nutritional supplement, achieved a perfect SUCRA of 100 percent for reducing Visual Analog Scale symptom ratings while simultaneously improving quality of life. Fermented red ginseng dominated the immunological endpoint, reducing serum immunoglobulin E levels with a SUCRA of 99.7 percent—a finding of mechanistic interest because IgE is the antibody class central to the allergic cascade, binding to mast cells and triggering histamine release upon allergen exposure. Flos Magnoliae volatile oil, derived from the flower buds used in traditional Chinese medicine for nasal obstruction, ranked highest at lowering serum eosinophil counts, with a SUCRA of 80.6 percent. Eosinophils are white blood cells recruited to inflamed nasal tissue in allergic disease, and their reduction signals a dampening of the underlying inflammatory process rather than merely masking symptoms.

Perhaps the most complete immunological result came from Phlai, a Thai ginger-family rhizome (Zingiber cassumunar), which achieved a perfect SUCRA of 100 percent for reducing interleukin-5 levels. IL-5 is the key cytokine driving eosinophil maturation, activation and survival, positioning Phlai upstream in the inflammatory hierarchy. Together, these biomarker findings sketch a plausible biological picture: several of the top-performing botanicals appear to act on the T helper 2-skewed immune signaling that underlies allergic rhinitis, modulating cytokines such as IL-4, IL-5 and IL-13, the NF-κB transcriptional pathway, and downstream effectors including eosinophils, leukotrienes and IgE.

The authors conclude that tomato extract, Glycyrrhiza glabra extract, spirulina, fermented red ginseng, Flos Magnoliae volatile oil and Phlai demonstrate more favorable efficacy profiles than the other plant-derived interventions in improving symptoms and quality of life. The study protocol was prospectively registered on PROSPERO (CRD420251052539), and the review’s breadth—spanning 24 substances and multiple laboratory indicators including interleukins, tumor necrosis factor-alpha, interferon-gamma and toll-like receptor signaling markers—makes it a valuable roadmap for prioritizing future trials.

Cautions remain, however. Network meta-analyses inherit the limitations of their component trials, which in this field often involve small samples, heterogeneous dosing, variable extract standardization and short follow-up periods. The certainty of evidence for individual comparisons can vary substantially, and indirect rankings should be read as hypothesis-generating rather than definitive prescriptions. The researchers note no competing interests, and the work was funded by the Department of Traditional Chinese Medicine Otorhinolaryngology of Shanxi University of Traditional Chinese Medicine and the Scientific Research Project of Shanxi Provincial Health Commission.

Even with those caveats, the analysis arrives at a moment of genuine clinical need. Allergic rhinitis prevalence continues to climb globally, and patients increasingly seek adjunctive or alternative options with favorable safety profiles. If larger, well-designed randomized trials confirm the rankings reported here—particularly for tomato extract on nasal symptoms and spirulina on patient-rated outcomes—everyday dietary and herbal compounds could earn a more rigorous, evidence-based place alongside conventional therapy. The study, published open access on 10 September 2026, invites both clinicians and researchers to look more closely at the pharmacological potential hiding in ordinary plants.

Subject of Research: Network meta-analysis of plant-derived active substances for the treatment of allergic rhinitis

Article Title: Active substances of plants in the treatment of allergic rhinitis: a systematic review and network meta-analysis

Article References: Fan, R., Li, Z., Liang, M., Wang, X., Zhao, C., & Zhang, Z. (2026). Active substances of plants in the treatment of allergic rhinitis: a systematic review and network meta-analysis. BMC Complementary Medicine and Therapies. https://doi.org/10.1186/s12906-026-05571-4

Image Credits: AI Generated

DOI: 10.1186/s12906-026-05571-4

Keywords: allergic rhinitis, plant extracts, network meta-analysis, spirulina, tomato extract, fermented red ginseng, Glycyrrhiza glabra, Flos Magnoliae volatile oil, Phlai, immunoglobulin E, interleukin-5, randomized controlled trials