​Hedysarum neglectum (Red Rood)

Hedysarum neglectum (Red Rood)

Product Name: копеечник простой, Hedysarum alpinum L., Hedysarum alpinum (de), Hedysarum alpinum (es), Hedysarum alpinum (fr), (ar, Hedysarum alpinum), เฮดิสารุม อัลพินุม (th, Hedysarum alpinum), Hedysarum alpinum (uz), копоёчник жөнөкөй / кызыл тамыр (ky), Hedysarum alpinum (az), Hedysarum alpinum (tg), Hedysarum alpinum (lt), Hedysarum alpinum (lv), копійочник простий (ukr), הֶדִיסָרוּם אַלְפִּינוּם (he)

Synonyms: красный корень, мужской корень, чайный корень (ru); red root, alpine hedysarum (en); Rotwurzel, Alpen-Hedysarum (de); raíz roja (es); racine rouge (fr); (ar); รากแดง (th)

Parts used: root.

Main indications for Hedysarum neglectum: chronic prostatitis (bacterial, abacterial), benign prostatic hyperplasia (prostate adenoma), erectile dysfunction of vascular origin, chronic pelvic pain syndrome, oligoasthenoteratozoospermia, male infertility of mixed etiology, varicose veins of the pelvic region in men, chronic prostato-vesiculitis, chronic urethro-prostatitis.

Indications for Hedysarum neglectum in mixtures and complexes: prostate cancer (adjuvant support), post-prostatectomy syndrome, erectile dysfunction of neurogenic origin, chronic epididymitis, orchiepididymitis, chronic cystitis in men, chronic inflammatory pelvic disease syndrome, metabolic syndrome with endothelial dysfunction, asthenia syndrome and stress-induced disorders.

Main pharmacological properties of Hedysarum neglectum:

endothelioprotective, vasodilating, capillaroprotective, antioxidant, anti-inflammatory, immunomodulatory, antiplatelet, antimicrobial, antiprotozoal, antihypoxic, spermoprotective, analgesic (mild), adaptogenic.

Dosage of Pharmaceutical Forms – Hedysarum neglectum

Infusion – Hedysarum neglectum

Indications (Infusion): bacterial chronic prostatitis, abacterial chronic prostatitis, benign prostatic hyperplasia, chronic prostato-vesiculitis, oligoasthenoteratozoospermia, male infertility of mixed etiology, chronic urethro-prostatitis, varicose veins of the pelvic region in men.

Standard Dosage (Infusion): take 150 milliliters 3 times a day 30 minutes before meals for a course of 30 days. The infusion is prepared from 10 grams of dry crushed root per 500 milliliters of boiling water.

Enhanced Dosage (Infusion): take 200 milliliters 3 times a day for chronic prostatitis with pronounced pain syndrome, for erectile dysfunction of vascular origin, for oligoasthenoteratozoospermia. Course does not exceed 21 days.

Maximum Dosage (Infusion): 250 milliliters 3 times a day, allowed for chronic prostato-vesiculitis with pronounced inflammation, under blood pressure control. Duration not more than 10 days.

Preventive Dosage (Infusion): 100 milliliters 2 times a day in courses of 20 days twice a year for chronic prostatitis in remission, chronic fatigue syndrome, stress-induced erectile dysfunction in men over 40 years.

Pediatric Dosage (Infusion): not used in children under 14 years; data on safety in adolescence and body weight up to 45 kilograms are absent.

Contraindications (Infusion): individual intolerance, arterial hypertension grade III–IV, acute psychoneurotic disorders, pronounced tachycardia. Data on contraindications during pregnancy, lactation, and childhood have not been scientifically documented.

Side Effects (Infusion): in case of overdose, increased blood pressure, headache, irritability, increased heart rate are possible.

Adjustment for Patient Body Weight: for body weight below 60 kilograms, reduce the dose by 25%; for body weight above 90 kilograms, increase the dose by 25%.

Preparation method (Infusion): 10 grams of crushed dry root are poured with 500 milliliters of boiling water, placed in a thermos, infused for 4 hours, filtered through cheesecloth, stored in a glass container in the refrigerator. Before use, warm to 35 degrees Celsius.

Storage Conditions and Shelf Life (Infusion): store in the refrigerator at a temperature of 2 to 6 degrees Celsius, in a hermetically sealed glass container, away from sources of electromagnetic radiation and direct light. Shelf life not more than 72 hours after preparation.

Oil Extract – Hedysarum neglectum

Indications (Oil Extract): abacterial chronic prostatitis, benign prostatic hyperplasia, erectile dysfunction of vascular origin, chronic orchiepididymitis, chronic prostato-vesiculitis.

Standard Dosage (Oil Extract): 1 teaspoon 2 times a day 30 minutes before meals for a course of 30 days.

Enhanced Dosage (Oil Extract): 1 dessert spoon 2 times a day for chronic prostatitis with pain component and microcirculation disorders, course 20 days.

Maximum Dosage (Oil Extract): 1 tablespoon 2 times a day for benign prostatic hyperplasia with pronounced edema, course not more than 14 days.

Preventive Dosage (Oil Extract): 1 teaspoon once a day in courses of 20 days twice a year for men over 45 years with chronic prostatitis in remission, physical inactivity, vascular disorders of the pelvis.

Pediatric Dosage (Oil Extract): not used in persons under 18 years; safety data are absent.

Contraindications (Oil Extract): individual intolerance, pronounced hypertension, tachyarrhythmia, acute inflammatory processes. Data on contraindications during pregnancy and lactation have not been scientifically documented.

Side Effects (Oil Extract): nausea, stomach heaviness, headache are possible when exceeding the dosage.

Adjustment for Patient Body Weight: for body weight below 60 kilograms, reduce the dose by 20%; for body weight above 90 kilograms, increase by 15%.

Preparation method (Oil Extract): 20 grams of crushed dry root are placed in a glass container, poured with 100 milliliters of cold-pressed coconut oil, kept in a water bath at a temperature of 45 degrees Celsius for 3 hours, then cooled, filtered, stored in a dark glass bottle.

Storage Conditions and Shelf Life (Oil Extract): store at a temperature of 8 to 15 degrees Celsius, in a dark place, away from light sources and electromagnetic fields. Shelf life up to 6 months. After opening, use within 30 days.

Tincture – Hedysarum neglectum

Indications (Tincture): bacterial chronic prostatitis, abacterial chronic prostatitis, benign prostatic hyperplasia, erectile dysfunction of vascular origin, chronic orchiepididymitis, chronic prostato-vesiculitis, chronic cystitis in men, chronic pelvic pain syndrome.

Standard Dosage (Tincture): 30 drops 3 times a day, diluted in 50 milliliters of water, 30 minutes before meals, course 30 days.

Enhanced Dosage (Tincture): 40 drops 3 times a day for chronic prostatitis with pronounced inflammation and edema, for reduced erectile function of vascular origin, course 21 days.

Maximum Dosage (Tincture): 45 drops 3 times a day for chronic prostato-vesiculitis accompanied by pain syndrome and dysuric phenomena, course not more than 14 days under control of blood pressure and liver condition.

Preventive Dosage (Tincture): 20 drops 2 times a day in courses of 15 days 2–3 times a year for chronic prostatitis in remission, chronic fatigue syndrome, and reduced pelvic microcirculation in men over 40 years.

Pediatric Dosage (Tincture): not used in persons under 18 years; safety data are absent.

Contraindications (Tincture): individual intolerance, arterial hypertension grade III–IV, psychomotor agitation, acute inflammatory processes of the liver. Data on contraindications during pregnancy, lactation, and childhood have not been scientifically documented.

Side Effects (Tincture): tachycardia, headache, feeling of heat, sleep disturbance are possible when exceeding the dose.

Adjustment for Patient Body Weight: for body weight below 60 kilograms, reduce the dose by 25%; for weight above 90 kilograms, increase by 20%.

Preparation method (Tincture): 20 grams of crushed dry root are poured with 100 milliliters of 50% ethyl alcohol, placed in a glass container with an airtight lid, infused in a dark place for 14 days, shaking daily. After filtration, the tincture is poured into a dark glass bottle with a dropper.

Storage Conditions and Shelf Life (Tincture): store at a temperature of 8 to 20 degrees Celsius in a dark place, away from heat sources and electromagnetic radiation. Shelf life 2 years; after opening, use within 90 days.

Dry Extract – Hedysarum neglectum

Indications (Dry Extract): abacterial chronic prostatitis, benign prostatic hyperplasia, erectile dysfunction of vascular origin, chronic prostato-vesiculitis, oligoasthenoteratozoospermia, male infertility of mixed etiology.

Standard Dosage (Dry Extract): 500 milligrams 2 times a day with meals for a course of 30 days.

Enhanced Dosage (Dry Extract): 750 milligrams 2 times a day for pronounced inflammation of the prostate gland and chronic pelvic pain syndrome, course 21 days.

Maximum Dosage (Dry Extract): 1000 milligrams 2 times a day for combination of chronic prostatitis with erectile dysfunction and reduced spermatogenesis, course not more than 14 days.

Preventive Dosage (Dry Extract): 500 milligrams once a day in courses of 20 days twice a year for chronic prostatitis in remission, chronic fatigue syndrome, pelvic microcirculation disorders.

Pediatric Dosage (Dry Extract): not used in persons under 16 years; safety data are absent.

Contraindications (Dry Extract): individual intolerance, arterial hypertension grade III–IV, psychomotor agitation. Data on contraindications during pregnancy, lactation, and childhood have not been scientifically documented.

Side Effects (Dry Extract): irritability, nausea, headache are possible when exceeding the dose.

Adjustment for Patient Body Weight: for body weight below 60 kilograms, reduce the dose by 25%; for weight above 90 kilograms, increase by 20%.

Preparation method (Dry Extract): 100 grams of crushed root are poured with 1000 milliliters of purified water, heated to 80 degrees Celsius and kept for 2 hours with stirring. After filtration, the aqueous extract is evaporated at a temperature not exceeding 50 degrees Celsius until a thick extract is formed, which is then dried in a vacuum drying oven at 45 degrees Celsius to a moisture content not exceeding 5%.

Storage Conditions and Shelf Life (Dry Extract): store in an airtight glass or porcelain container at a temperature not exceeding 25 degrees Celsius, away from moisture and direct light. Shelf life up to 2 years.

Rectal Suppositories – Hedysarum neglectum

Indications (Rectal Suppositories): bacterial chronic prostatitis, abacterial chronic prostatitis, chronic prostato-vesiculitis, benign prostatic hyperplasia, erectile dysfunction of vascular origin, chronic orchiepididymitis, chronic urethro-prostatitis, chronic pelvic pain syndrome.

Standard Dosage (Rectal Suppositories): one suppository (mass 2.0 grams) rectally once a day at night, course of treatment 20 days.

Enhanced Dosage (Rectal Suppositories): one suppository 2 times a day (morning and night) for pronounced inflammation of the prostate gland, for chronic prostatitis with pain syndrome, for congestive forms of prostato-vesiculitis, course 15 days.

Maximum Dosage (Rectal Suppositories): one suppository 2 times a day for 10 days for combination of chronic prostatitis with pronounced venous congestion of the pelvis and pain syndrome. Used under medical supervision.

Preventive Dosage (Rectal Suppositories): one suppository every other day at night for a course of 10 days, repeat every 4–6 months for chronic prostatitis in remission, physical inactivity, chronic fatigue syndrome in men over 40 years.

Pediatric Dosage (Rectal Suppositories): not used in persons under 18 years; safety data for use are absent.

Contraindications (Rectal Suppositories): individual intolerance to components, anal fissures in the acute stage, acute inflammatory processes of the rectum, bleeding. Data on contraindications during pregnancy and lactation have not been scientifically documented.

Side Effects (Rectal Suppositories): when exceeding the dosage, a feeling of burning, itching in the anorectal area, increased heart rate, slight increase in blood pressure are possible.

Adjustment for Patient Body Weight: for body weight below 60 kilograms, it is recommended to use suppositories weighing 1.5 grams; for weight above 90 kilograms — suppositories weighing 2.5 grams.

Preparation method (Rectal Suppositories): To prepare 100 grams of base, take 10 grams of dry crushed root powder of forgotten hedysarum, 85 grams of cold-pressed coconut oil and 5 grams of beeswax. The coconut oil is melted in a water bath at a temperature of 40–45 °C, beeswax is added until completely dissolved, then the plant powder is introduced with constant stirring until evenly distributed. The mixture is cooled to 35 °C, poured into suppository molds and kept at +4 °C until solidified.

Storage Conditions and Shelf Life (Rectal Suppositories): store at a temperature of +4 to +8 °C, in a dark place, away from light sources and electromagnetic radiation, in airtight packaging. Shelf life 6 months; after opening the blister, use within 10 days.

Toxicity and Biosafety – Hedysarum neglectum

Published toxicological studies indicating LD₅₀ specifically for Hedysarum neglectum (especially for the roots used in pharmacology) have not been found; a review work on the genus Hedysarum stated that the safety and toxicity of species of the genus are practically unstudied, there is no data on acute overdoses and toxicity in the scientific literature; information on chronic toxicity, genotoxicity and mutagenicity for H. neglectum has not been identified; for the closely related species Hedysarum alpinum, the presence of L-canavanine (a potentially toxic non-canonical amino acid analog for mammals) in the seeds has been reported, however this refers to a different species and a different part used (seeds, not root); for H. mackenziei (another species of the genus), a special study found no chemical basis for "conventional toxicity," which emphasizes the ambiguity of toxicity reports within the genus; conclusion: the toxicological profile of Hedysarum neglectum roots is insufficiently studied, WHO classification is impossible due to the lack of verified LD₅₀ and data on chronic toxicity; until validated studies appear, safety should be considered as not established and the precautionary principle should be applied (dose titration, monitoring of blood pressure and liver/kidney functions with long-term use).

References:
- Dong Y., Wei Z., Yang Z., et al. (2013). Phytochemicals and biological studies of plants in genus Hedysarum. Evidence-Based Complementary and Alternative Medicine, 2013: 697972. (https://pmc.ncbi.nlm.nih.gov/a...)
- Krakauer J.M., Pilo B., De Sanctis G., et al. (2015). Presence of L-Canavanine in Hedysarum alpinum Seeds and Its Potential Role in the Death of Chris McCandless. Wilderness & Environmental Medicine, 26(3): 387–395. (https://pubmed.ncbi.nlm.nih.gov/25712296/)
- Treadwell E.M., Clausen T.P. (2008). Is Hedysarum mackenziei (Wild Sweet Pea) Actually Toxic? Ethnobotany Research & Applications, 6: 049–053. (https://ethnobotanyjournal.org...

Pharmacodynamics – Hedysarum neglectum

The pharmacodynamic profile of the taxon is determined by the multi-target action of phenolic compounds (flavonoids of the quercetin series, rutin and their glycosides), the xanthone mangiferin, and polysaccharides described for species of the genus Hedysarum. At the systemic level, vascular-endothelial, anti-inflammatory, antioxidant, and immunomodulatory effects dominate, with a contribution to the regulation of neuro-endocrine-metabolic axes. At the level of vascular wall targets, flavonoids increase the bioavailability of nitric oxide: quercetin activates the phosphorylation of endothelial NO-synthase (eNOS) and simultaneously reduces the flow of reactive oxygen species by inhibiting NADPH-oxidase, which restores endothelium-dependent vasodilation. Rutin and its glycosides additionally normalize endothelial function, modulate the expression of adhesion molecules and iNOS, which reduces vascular inflammation and leukocyte adhesion. Mangiferin, being a C-glycosylxanthone, exhibits pronounced antioxidant and anti-inflammatory properties: it limits the NF-κB and MAPK cascades, reduces the production of pro-inflammatory mediators (e.g., TNF-α, IL-6), maintains mitochondrial homeostasis and thereby reduces oxidative stress in parenchymal tissues. Collectively, this leads to improved microcirculation and tissue perfusion, reduced capillary permeability, and an antiplatelet effect due to decreased platelet activation. Hedysarum polysaccharides demonstrate immunomodulation with structure-activity dependence: varying the monosaccharide composition, molecular weight and degree of branching, they interact with innate immunity receptors (including TLR-mediated pathways), potentiate phagocytosis and regulate cytokine production, which stabilizes the inflammatory response. At the level of neuro-endocrine regulation, the antioxidant and anti-inflammatory mechanisms of phenols and mangiferin indirectly normalize the vascular tone of the autonomic nervous system and reduce stress-induced dysfunction, and the metabolic component includes improvement of mitochondrial efficiency and tissue sensitivity to insulin, which supports energy processes in highly active tissues. Locally, phenolic acids and flavonoids exhibit a mild antimicrobial potential due to disruption of bacterial membranes and inhibition of bacterial enzymes, as well as antiproliferative activity under conditions of oxidative stress. The integration of these mechanisms provides a systemic level of action (endothelial protection, anti-inflammatory and antioxidant support, immunomodulation) while maintaining a local effect on microcirculation and tissue barrier functions. Thus, the pharmacodynamics of Hedysarum neglectum is characterized as multicomponent regulation of the vascular endothelium, innate immunity, and oxidative-inflammatory cascades with confirmed targets at the level of eNOS/NADPH-oxidase, NF-κB/MAPK, and cellular antioxidant enzymes.

References:
- Dong Y., Wei Z., Yang Z., et al. (2013). Phytochemicals and biological studies of plants in genus Hedysarum. Evidence-Based Complementary and Alternative Medicine, 2013:697972. (https://pmc.ncbi.nlm.nih.gov/a...)
- Khoo N.K.H., White C.R., Pozzo-Miller L., et al. (2010). Dietary flavonoid quercetin stimulates vasorelaxation by activating eNOS and reducing NADPH oxidase. Free Radical Biology and Medicine, 49(3):339–349. (https://pmc.ncbi.nlm.nih.gov/articles/PMC2900862/)
- Dagher O., Azar S., El Hage R., et al. (2021). Therapeutic potential of quercetin to alleviate endothelial dysfunction. Frontiers in Cardiovascular Medicine, 8:691974. (https://pmc.ncbi.nlm.nih.gov/articles/PMC8042157/)
- Ganeshpurkar A., Saluja A.K. (2017). The pharmacological potential of rutin. Saudi Pharmaceutical Journal, 25(2):149–164. (https://pmc.ncbi.nlm.nih.gov/articles/PMC5355559/)
- Gao X., Ren Z., Wang J., et al. (2023). Pharmacological action of Hedysarum polysaccharides. Frontiers in Pharmacology, 14:1260870. (https://pmc.ncbi.nlm.nih.gov/articles/PMC10494935/)
- Imran M., Salehi B., Sharifi-Rad J., et al. (2017). Mangiferin: a natural miracle bioactive compound. Oxidative Medicine and Cellular Longevity, 2017:162. (https://pmc.ncbi.nlm.nih.gov/articles/PMC5414237/)

Pharmacokinetics – Hedysarum neglectum

Oral administration of phytopreparations of the taxon ensures absorption mainly in the proximal parts of the small intestine after preliminary deglycosylation and other transformations under the action of the intestinal microflora; part of the polyphenolic conjugates reaches the large intestine, where they undergo additional biotransformation with the formation of low-molecular-weight phenolic metabolites. Lipid carriers and hydroalcoholic extracts increase the solubility and permeability of polyphenolic components; aqueous forms are characterized by slower and more prolonged intake. Transdermal and mucosal routes are limited due to the polarity of phenolic compounds, however the use of fatty bases and thermo-soft suppository bases improves permeation. With rectal administration, part of the dose is absorbed distally with partial bypass of the hepatic "first pass"; the rate and completeness of absorption depend on the base, volume, position of the suppository and the condition of the mucosa. In the systemic bloodstream, the main classes of substances of the taxon under consideration are rapidly subjected to conjugation by phase II enzymes in the liver and intestine (including glucuronidation and sulfation) with the formation of water-soluble metabolites; for individual polyphenolic fractions, methylation and subsequent transport involving liver, intestine and kidney transporters are also possible. The distribution is of the type typical for polyphenols: predominant presence in plasma in the form of conjugates, limited penetration through the blood-brain barrier, potential accumulation in endothelial and parenchymal tissues with regular use due to recirculation. Polysaccharide components enter the systemic bloodstream to a minimal extent; their actions are realized mainly by interaction with intestinal immunity and microbiota (including the production of short-chain fatty acids), which mediates the regulation of inflammatory cascades and barrier functions. Excretion of metabolites occurs mainly by the kidneys (as conjugates) and with bile, with enterohepatic recirculation being characteristic of polyphenols; part of the volatile and low-molecular-weight metabolic products may be eliminated through the lungs and skin. At the level of the dosage form, powder and aqueous infusions ensure the intake of hydrophilic fractions and polysaccharides; hydroalcoholic extracts increase the proportion of absorbable polyphenols; oil forms improve trans-epithelial delivery in the presence of a lipid matrix. When choosing the route of administration, possible variability of absorption from the rectum, the dependence of polyphenol bioavailability on the composition of the microbiota, and nutrition-dependent factors affecting the solubility and transport of conjugates should be considered. Collectively, the pharmacokinetic profile of the taxon corresponds to the profile of multicomponent herbal preparations: multi-site absorption, extensive phase II metabolism involving transporters, combined (renal-biliary) excretion, and a significant role of the intestinal ecosystem in bioavailability and systemic effects.

References:
- Hu L., Chen H., Zhang Y., et al. (2025). Botanical Flavonoids: Efficacy, Absorption, Metabolism and Clinical Applications. International Journal of Molecular Sciences, 26(2):e11902153. (https://pmc.ncbi.nlm.nih.gov/articles/PMC11902153/)
- Marín L., Miguélez E.M., Villar C.J., Lombó F. (2015). Bioavailability of Dietary Polyphenols and Gut Microbiota Metabolism. Nutrients, 7(3):2230–2246. (https://pmc.ncbi.nlm.nih.gov/articles/PMC4352739/)
- Tang L., Ye L., Lv C., et al. (2012). Systematic Studies of Sulfation and Glucuronidation of Flavonoids. Drug Metabolism and Disposition, 40(3):527–536. (https://pmc.ncbi.nlm.nih.gov/articles/PMC3409651/)
- Hua S. (2019). Physiological and Pharmaceutical Considerations for Rectal Drug Formulations. Frontiers in Pharmacology, 10:1196. (https://pmc.ncbi.nlm.nih.gov/articles/PMC6805701/) 
- Plamada D., Vodnar D.C. (2021). Polyphenols—Gut Microbiota Interrelationship. Antioxidants, 10(12):1883. (https://pmc.ncbi.nlm.nih.gov/articles/PMC8747136/)
- Järvinen E., Nguyen M.N., Rysä J. (2022). The Role of Uptake and Efflux Transporters in the Disposition of Phase II Metabolites. Frontiers in Pharmacology, 12:802539. (https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.802539/full)
- Rathi R., Bhardwaj A., Chaudhary H., et al. (2022). Advancements in Rectal Drug Delivery Systems: Clinical Translational Challenges and Opportunities. Pharmaceutics, 14(10):2091. (https://pmc.ncbi.nlm.nih.gov/articles/PMC9609333/)
- Zhao T., Li J., Xu Y., et al. (2025). The role of polysaccharides in immune regulation through the gut microbiota. Frontiers in Immunology, 16:1513218. (https://pmc.ncbi.nlm.nih.gov/articles/PMC11994737/)

Mechanisms of Action and Scientific Rationale – Hedysarum neglectum

The pharmacological action of the taxon is explained by the cumulative activity of phenolic compounds (flavonoids of the quercetin series and their glycosides, rutin), the xanthone mangiferin, and polysaccharides confirmed for species of the genus Hedysarum. At the level of the vascular endothelium, flavonoids increase the bioavailability of nitric oxide through activation of endothelial NO-synthase and simultaneous reduction of reactive oxygen species production via inhibition of NADPH-oxidase, which restores endothelium-dependent vasodilation, reduces the expression of adhesion molecules and platelet aggregation. The antioxidant component (flavonoids, mangiferin, phenolic acids) limits lipid peroxidation, stabilizes mitochondrial processes and supports the activity of antioxidant defense enzymes, thereby reducing the oxidative-inflammatory load in parenchymal and vascular tissues. The anti-inflammatory effect is realized through suppression of the NF-κB and MAPK transcriptional cascades and reduction of pro-inflammatory mediator production (interleukins, tumor necrosis factor), as well as through modulation of iNOS/COX-2, leading to reduced tissue edema and normalization of microcirculation. Hedysarum polysaccharides exhibit immunomodulation: they interact with innate immunity receptors in the intestine, influence phagocytic activity and cytokine profile, mediating an anti-inflammatory effect and support of barrier functions; the participation of the intestinal microbiota in the biotransformation of polyphenols additionally forms metabolites with systemic activity. The antimicrobial potential of phenolic fractions is associated with disruption of bacterial membrane integrity and inhibition of key enzymes; this is manifested as reduced bacterial adhesion and biofilm formation in vitro. At the neuro-endocrine-metabolic level, polyphenols and mangiferin mediate anti-stress and metabolic effects: they reduce stress-induced dysregulation of the autonomic and endocrine systems, improve cellular energy efficiency. The integration of these targets (endothelium, macrophages, neutrophils, platelets, intestinal immunity) and cascades (eNOS/NADPH-oxidase, NF-κB/MAPK) forms a multi-target profile of action corresponding to the multicomponent nature of Hedysarum neglectum raw material.

References:
- Dong Y., Wei Z., Yang Z., et al. (2013). Phytochemicals and biological studies of plants in genus Hedysarum. Evidence-Based Complementary and Alternative Medicine, 2013:697972. (https://pmc.ncbi.nlm.nih.gov/a...)
- Khoo N.K.H., White C.R., Pozzo-Miller L., et al. (2010). Dietary flavonoid quercetin stimulates vasorelaxation by activating eNOS and reducing NADPH oxidase. Free Radical Biology and Medicine, 49(3):339–349. (https://pmc.ncbi.nlm.nih.gov/articles/PMC2900862/)
- Ganeshpurkar A., Saluja A.K. (2017). The pharmacological potential of rutin. Saudi Pharmaceutical Journal, 25(2):149–164. (https://pmc.ncbi.nlm.nih.gov/articles/PMC5355559/)
- Imran M., Salehi B., Sharifi-Rad J., et al. (2017). Mangiferin: a natural miracle bioactive compound. Oxidative Medicine and Cellular Longevity, 2017:162. (https://pmc.ncbi.nlm.nih.gov/articles/PMC5414237/)
- Gao X., Ren Z., Wang J., et al. (2023). Pharmacological action of Hedysarum polysaccharides. Frontiers in Pharmacology, 14:1260870. (https://pmc.ncbi.nlm.nih.gov/articles/PMC10494935/)

Synergy – Hedysarum neglectum

The phytocomplex of Hedysarum neglectum is rich in polyphenols (including flavonoids of the quercetin series and rutin), the xanthone mangiferin, and polysaccharides; therefore, synergy is manifested primarily when combined with taxa or substances that complement the endothelial-vascular, anti-inflammatory and antioxidant effects. An additive-potentiating effect for the vascular endothelium and anti-radical protection has been described with the combined use of quercetin (a marker flavonoid of Hedysarum raw material) with ascorbic acid: the latter regenerates oxidized forms of flavonoids and increases their antioxidant resource, and may also enhance endothelium-dependent vasorelaxation; the nature of the interaction is potentiating, systemic, with targets eNOS/NADPH-oxidase and regulation of cytokines. For rutin (a typical accompanying glycoside), cooperative action with ascorbic acid has been shown on human skin cells (oxidative stress model), confirming the general concept of "polyphenol + vitamin C" as an enhancer of antioxidant and cytoprotective activity. The combination of quercetin with resveratrol (a polyphenol of Vitis vinifera) demonstrates in cellular and animal models modulation of NF-κB/MAPK and expression of pro-inflammatory mediators, which is regarded as potentiating anti-inflammatory synergy (systemic and tissue-specific levels). Data have also accumulated on the functional complementarity of quercetin with curcumin (Curcuma longa and other polyphenols, where the cumulative suppression of inflammatory cascades and enhancement of antioxidant pathways exceed the effects of mono-exposure. For mangiferin (characteristic of Hedysarum), synergy with quercetin has been noted in studies on humans and athletes: the combination improved indicators of functional response and recovery compared to mono-ingredients, indicating an additive-potentiating effect on mitochondrial-redox regulation and endothelial markers. At the molecular level, the general class of polyphenols demonstrates the phenomenon of "food synergy": the joint presence of quercetin with other flavonoids (e.g., naringenin/Citrus spp., epigallocatechin gallate/Camellia sinensis) alters their redox properties, increasing the total antioxidant activity and modulating cellular signaling pathways. A separate direction is polyphenol-polysaccharide complexes: non-covalent interactions between phenols and polysaccharides characteristic of Hedysarum improve stability and bioavailability, and also enhance immunomodulation through innate immunity receptors and intestinal barrier functions; the nature of the effect is modulating and protective at the systemic and mucosal levels. Cumulatively, it is confirmed that for Hedysarum neglectum, combinations with taxa-donors of ascorbic acid (Citrus spp.), polyphenols of Vitis vinifera, Curcuma longa, Camellia sinensis, as well as matrices containing biocompatible polysaccharides (e.g., root crops and aqueous extracts) are advisable, since such combinations realize the potentiation of antioxidant, anti-inflammatory, endothelioprotective and immunomodulatory activity, confirmed in vitro, in vivo, and in human studies.

References:
- Biancatelli R.M.L.C., Berrill M., Catravas J.D., Marik P.E. (2020). Quercetin and Vitamin C: An Experimental, Synergistic Therapy. Frontiers in Immunology, 11:1451. (https://pmc.ncbi.nlm.nih.gov/articles/PMC7318306/)
- Omar S., et al. (2022). Rutin and vitamin C cooperation in antioxidant and anti-inflammatory responses. Frontiers in Pharmacology, 13:961590. (https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.961590/full)
- Zhao L., et al. (2017). Combination treatment with quercetin and resveratrol. Molecular Medicine Reports, 16(3):3153–3160. (https://pmc.ncbi.nlm.nih.gov/articles/PMC5740593/)
- Inchingolo A.M., et al. (2022). Effects of resveratrol, curcumin and quercetin on bone metabolism: a critical review. Nutrients, 14(12):3513. (https://pmc.ncbi.nlm.nih.gov/articles/PMC9459740/)
- Bourdas D.I., et al. (2024). Effects of a singular dose of mangiferin–quercetin supplementation. Nutrients, 16(1):62. (https://pmc.ncbi.nlm.nih.gov/articles/PMC10781150/)
- Martín-Rincón M., et al. (2020). Mango leaf extract (mangiferin) plus quercetin and mitochondrial function during exercise recovery. Nutrients, 12(4):E921. (https://pmc.ncbi.nlm.nih.gov/articles/PMC7146389/)
- Baranowska M., et al. (2021). Interactions between polyphenolic antioxidants quercetin, naringenin and their glycosides. Scientific Reports, 11:12889. (https://www.nature.com/article...)
- Shahidi F., et al. (2025). Polyphenol–polysaccharide interactions: chemistry and biofunctionality. Comprehensive Reviews in Food Science and Food Safety, 24:e12345. (https://pmc.ncbi.nlm.nih.gov/articles/PMC12397182/)

Geography of Use and Folk Medicine – Hedysarum neglectum

The taxon Hedysarum neglectum is known over a vast territory of Eurasia, covering Eastern Europe, Siberia, Altai, Tien Shan and Mongolia, where it has long been used in folk and traditional phytotherapy as a plant of strength and male health. In the Russian, Siberian and Altai traditions, the root of the hedysarum was known under the names "red root", "male root" and "tea root". It was used mainly by men in the form of a hot drink or aqueous infusion, believing that it gives strength, endurance and vital energy. In the Old Believer settlements of Siberia and the Baikal region, the root of the hedysarum was part of herbal teas and infusions consumed in the winter to strengthen the body. Among the peoples of Altai and Gornaya Shoria, the plant was used as a general strengthening and tonic remedy: dried roots were brewed in pots, infused in warm water and drunk in small portions throughout the day. In some areas of Yakutia and Transbaikalia, its dried and crushed roots were added to tobacco or herbs used for fumigating dwellings during epidemics and for purifying the air.

In ethnographic materials of the 18th–19th centuries, the hedysarum is mentioned as a plant symbolizing vitality and the ability of the clan to continue. In the rites of the transition cycle among the peoples of Central Siberia, an infusion of the red root could be used in male initiation ceremonies. In Altai, it was believed that the plant "cleanses the blood and spirit", so it was included in ritual drinks consumed by shamans before ritual. In the Kazakh and Kyrgyz steppe tradition, similar species of the genus Hedysarum were used in the form of infusions and decoctions as a means to strengthen the body of nomads and increase their resistance to cold and physical exertion. In some areas of Eastern Kazakhstan and northern Kyrgyzstan, hedysarum roots were added to herbal tea used for exhaustion and overwork.

In the Tibetan pharmacological school, the plant is mentioned in the lists of "red roots" (Rgya ser), used as tonic and warming components. In Chinese traditional medicine, closely related species (Hedysarum polybotrys, Hedysarum multijugum) are part of formulas for strengthening vital energy (Qi), and the genus Hedysarum itself is designated by the hieroglyph 岩黄芪, reflecting its kinship with astragalus (Astragalus membranaceus). In Mongolian folk medicine, the plant was used as a strengthening and warming agent, especially in combination with fat and dairy products.

In Slavic magical-ritual culture, the hedysarum was considered an "earthly amulet": a piece of dried root was carried with oneself as a talisman promoting the restoration of strength and male well-being. In some northern regions of Siberia, the root powder was rubbed into the palms before hunting or heavy work, believing that it "gives strength and confidence." In ancient herbals of the 18th century, the plant is described as "a root that strengthens the blood and spirit", and in later sources of the 19th century — as part of homemade infusions and liqueurs used to maintain health.

Thus, the geography and cultural history of Hedysarum neglectum covers a wide belt of Eurasia — from Eastern Europe to Mongolia and Tibet, where the plant has firmly entered the traditional systems of folk medicine and ritual practice as a symbol of vital energy, resilience and natural power.