Interleukin Modulation by Ayurvedic Herbs: Anti-Cytokine Storm Evidence

The term “cytokine storm” entered mainstream medical vocabulary during the COVID-19 pandemic, although immunologists had studied the phenomenon in influenza, sepsis, and autoimmune disease for decades. The hyperinflammatory immune response that characterises severe viral illness — in which IL-6, TNF-alpha, IL-1beta, and IFN-gamma escalate in a self-reinforcing cascade — became a focus of both new drug development and renewed interest in established anti-inflammatory agents. Laboratory and early clinical studies suggest that several plants used in Ayurveda interact with specific interleukin and cytokine pathways, though it must be stated plainly that most of this evidence remains preclinical and mechanistic rather than confirmatory.

This is not a claim that Ayurveda treats COVID-19 or any specific infectious disease. It is a pharmacological and classical review of documented mechanisms and traditional usage, presented with their appropriate clinical limits.

The Cytokine Storm: Mechanism and Targets

Under normal immune activation, dendritic cells and macrophages release cytokines that coordinate a measured inflammatory response. In cytokine storm this regulation fails: positive-feedback loops among IL-6, TNF-alpha, and IL-1beta create a self-amplifying cascade that injures healthy tissue, particularly the lung endothelium and vascular system. The principal therapeutic targets identified in the immunological literature include:

• IL-6: the primary driver of the acute-phase response; its receptor is the target of the monoclonal antibody tocilizumab used in severe COVID-19
• TNF-alpha: central to the NF-kB inflammatory pathway; elevated in sepsis, autoimmune conditions, and severe infection
• IL-1beta: activates the NLRP3 inflammasome, triggering pyroptosis and vascular leakage
• IFN-gamma: drives the macrophage activation syndrome associated with haemophagocytic lymphohistiocytosis
• NLRP3 inflammasome: the molecular platform on which IL-1beta maturation depends; an emerging drug target across multiple inflammatory conditions

Guduchi (Tinospora cordifolia): The Most Studied Ayurvedic Immunomodulator

Guduchi (giloy, Tinospora cordifolia) is among the most extensively investigated herbs of the Ayurvedic materia medica. Classical texts give it the name Amrita, “the nectar of immortality,” and Charaka places it among the Vayasthapana (age-sustaining), Trishna-nigrahana (thirst-relieving), and Dahaprashamana (heat-quelling) groups of herbs. Its rasa (taste) is tikta (bitter) and kashaya (astringent), its virya (potency) ushna (heating), and its vipaka (post-digestive effect) madhura (sweet); it is classically regarded as tridoshahara and as a premier Rasayana (rejuvenative) used to rebuild strength and resilience after illness.

Phytochemically, Tinospora contains several chemically distinct classes of constituent, which should not be conflated: isoquinoline-type alkaloids such as berberine, palmatine, and magnoflorine; diterpenoid furanolactones such as columbin and tinosporide; clerodane glycosides such as tinocordiside and cordifolioside; and an immunologically active arabinogalactan polysaccharide. Columbin is a bitter diterpenoid lactone, not an alkaloid, and berberine is a separate isoquinoline alkaloid — the two belong to different chemical families and are not interchangeable names for one compound. Experimental reviews of the plant attribute much of its immunomodulatory activity to the arabinogalactan polysaccharide and report that the herb acts bidirectionally rather than as a simple immunosuppressant: in immunodeficient models it enhances natural-killer-cell activity and macrophage phagocytosis, while in hyperinflammatory models it dampens pro-inflammatory cytokine output. This normalising, bidirectional character is consistent with the classical understanding of Guduchi as a Rasayana rather than a single-target drug.

In classical practice Guduchi is rarely given as a crude alkaloid. It is used as Guduchi Satva (the starch-like aqueous extract), as Samshamani Vati (also called Guduchi Ghana Vati, the solidified decoction), and within compound formulations such as Amritarishta and Guduchyadi Kashaya, classically indicated in Jvara (fever) — particularly Jirna Jvara, the chronic or lingering fever — as well as in Vatarakta and Prameha. These traditional indications align with the herb’s documented anti-inflammatory and immunomodulatory pharmacology, but rigorous human trials specific to cytokine-storm conditions are still lacking, and that gap should not be overstated.

Yashtimadhu (Glycyrrhiza glabra): Glycyrrhizin and HMGB1

Yashtimadhu (licorice root, Glycyrrhiza glabra; also Madhuyashti or Mulethi) is one of the most valued herbs of classical Ayurveda, included in Charaka’s Jivaniya (life-promoting), Kanthya (voice-improving), Varnya (complexion-improving), and Sandhaniya groups. Its rasa is madhura (sweet), its virya sheeta (cooling), and its vipaka madhura, and it is traditionally used as a Rasayana for the respiratory tract and throat. Its principal triterpenoid saponin, glycyrrhizin, has a well-characterised anti-inflammatory profile:

• It binds directly to HMGB1 (high-mobility group box 1 protein) and inhibits its cytokine activity — HMGB1 being a late-phase mediator that sustains inflammation after the initial infectious trigger has been controlled
• It is reported to reduce NLRP3 inflammasome activation, limiting IL-1beta maturation
• It modulates interferon and JAK-STAT signalling in experimental systems
• It inhibits phospholipase A2, reducing arachidonic-acid release and downstream prostaglandin and leukotriene production

Andrographis paniculata (Bhunimba / Kalamegha): The NF-kB and STAT3 Modulator

In Ayurveda Andrographis paniculata is known by the Sanskrit names Bhunimba (“neem of the ground,” for its intense bitterness) and Kalamegha; “Kalmegh” is the common Hindi and Bengali vernacular form rather than the classical Sanskrit or pharmacopoeial name. It is an intensely tikta (bitter) herb used classically as a deepana-pachana (digestion-kindling) agent and as a remedy for fever and liver disorders, especially in Pittaja jvara and in afflictions of the Yakrit (liver). Its primary diterpene lactone, andrographolide, has been studied as an inhibitor of the two transcription factors most central to cytokine-storm amplification, NF-kB and STAT3:

• It forms a covalent adduct with reduced cysteine 62 of the NF-kB p50 subunit, blocking the protein’s binding to DNA and thereby suppressing NF-kB-driven transcription
• It is reported to interfere with STAT3 activation, the pathway through which IL-6 propagates its inflammatory signal
• In cell-culture models it reduces replication of several respiratory viruses, an effect attributed in part to interference with viral protease activity

Andrographis has been evaluated in human trials for uncomplicated upper-respiratory-tract infection, where it has shown modest symptomatic benefit. Claims of dramatic benefit in COVID-19, however, are not supported by reliable randomised evidence; existing trials of standardised andrographolide doses have not demonstrated a consistent, clinically meaningful advantage, and the herb should not be presented as a proven antiviral therapy.

The Classical Formula Approach: Sudarshana Churna

Classical Ayurveda rarely treats Jvara (fever) with a single herb. Instead it relies on compound formulas (yoga) in which many bitter, deepana-pachana herbs are combined to digest Ama (undigested metabolic residue) and rebalance the doshas. Sudarshana Churna (in its larger form Mahasudarshana Churna), described in classical compendia such as the Bhaishajya Ratnavali, is among the most widely used Ayurvedic antipyretic formulas. Built around the intensely bitter Kiratatikta (Swertia chirata) together with Guduchi and a large number of supporting herbs, it is classically indicated in Vishama Jvara — the irregular, recurrent, and intermittent fevers that include malaria-like and chronic febrile patterns.

A related and frequently cited Tamil formula, Nilavembu Kudineer, is used for similar febrile and inflammatory conditions, but it belongs to the Siddha system — a distinct classical tradition of South India — and does not appear in the Ayurvedic classical texts or the Ayurvedic Pharmacopoeia of India; it should therefore not be described as an Ayurvedic formula. Within Ayurveda itself, the rationale for multi-herb antipyretics is the principle of synergy: bitter herbs such as Kiratatikta and Guduchi supply the central febrifuge and Ama-digesting action; aromatic and pungent additions such as dry ginger (Shunthi) and the Trikatu group act as deepana and as anupana that aid absorption; and the whole is held to function as a balanced pharmacological ensemble rather than as a single isolated molecule.

Safety Considerations for Cytokine-Modulating Herbs

Enthusiasm for cytokine-modulating herbs must be matched by explicit safety awareness, because several of these plants carry genuine risks at therapeutic doses:

• Yashtimadhu: glycyrrhizin raises blood pressure through mineralocorticoid-like activity and can cause hypokalaemia and fluid retention. It is contraindicated in uncontrolled hypertension and should not be taken at high doses for more than four to six weeks without medical supervision.
• Andrographis: animal studies suggest it may reduce sperm parameters at high doses, so it is best avoided by men actively trying to conceive; it may also potentiate anticoagulant and antiplatelet medicines.
• Guduchi: published case series have linked some commercial Tinospora cordifolia preparations to herb-induced liver injury, including an autoimmune-pattern hepatitis. Correct botanical identification and quality-verified sources are essential, and unexplained jaundice warrants stopping the herb and seeking medical care.
• Curcumin (Haridra): can inhibit platelet aggregation, warranting caution with anticoagulants, and inhibits CYP3A4, potentially altering the levels of many prescription medicines.

For anyone receiving immunosuppressive therapy for autoimmune disease or organ transplantation, cytokine-modulating herbs require careful medical supervision, because their effects on immune regulation may interact unpredictably with pharmaceutical immunosuppressants.

The immunological themes here connect to the broader Ayurvedic anti-inflammatory framework covered in the Ayurvedic anti-inflammatory diet. For further pharmacological context, the herb-drug interactions safety guide provides essential reference for herb-medication combinations.

This is a pharmacological and classical review for educational purposes only. None of the herbs or formulas described here should be used as a first-line treatment for COVID-19, sepsis, or any acute inflammatory condition requiring urgent medical care. Always consult a qualified healthcare provider and a registered Ayurvedic practitioner before using cytokine-modulating herbs, particularly if you take immunosuppressants, anticoagulants, or antiviral medicines.

References

1. Nejm (nejm.org)
2. Tinospora cordifolia (Willd.) Hook. f. and Thoms. (Guduchi) – validation of the Ayurvedic pharmacology through experimental and clinical studies (2010), PubMed Central
3. Glycyrrhizin binds to high-mobility group box 1 protein and inhibits its cytokine activities (2007), PubMed
4. Andrographolide attenuates inflammation by inhibition of NF-kappa B activation through covalent modification of reduced cysteine 62 of p50 (2004), PubMed
5. Profiling Inflammatory Biomarkers following Curcumin Supplementation: An Umbrella Meta-Analysis of Randomized Clinical Trials (2023), PubMed Central
6. NCBI