Andrographis

Metadata

Approved Indications

Commission E (Germany)

• No Commission E monograph exists for Andrographis paniculata. The herb was not part of the German phytotherapy tradition at the time of Commission E evaluations (1978-1994).

ESCOP

• No ESCOP monograph identified for Andrographis paniculata. [NEEDS-RESEARCH for latest ESCOP publications]

EMA/HMPC

• No EU herbal monograph adopted. The HMPC/MLWP assessed Andrographis paniculata Nees, folium and concluded that the requirements for establishing a Community herbal monograph for either traditional or well-established use were not fulfilled. A public statement was issued (EMA/HMPC/320433/2012).
• Reason for rejection: Lack of 30 years of documented traditional medicinal use in the EU (required for traditional use pathway), and insufficient clinical evidence meeting EU standards for well-established use pathway.

National Registrations

• Sweden: Kan Jang is registered as a traditional herbal medicinal product under Swedish national procedures
• Scandinavian countries: Various Andrographis-containing products registered nationally
• Thailand: Listed in the Thai National List of Essential Medicines for symptomatic relief of sore throat and common cold symptoms
• India: Part of Ayurvedic pharmacopoeia

Agreement/Disagreement

• Striking divergence: Clinical trial evidence is actually stronger for Andrographis (particularly Kan Jang) than for several herbs that DO have EU monographs (e.g., Eleuthero, E. angustifolia root). The regulatory gap reflects the EU framework’s bias toward European traditional heritage rather than global evidence.

Conditions Treated

• Upper respiratory tract infections (common cold, pharyngitis, tonsillitis)
• Sinusitis (acute, as adjunctive treatment)
• Uncomplicated influenza-like illness
• [Traditional/Ayurvedic]: Fever, liver disorders, intestinal infections, skin diseases, snake bites
• [Preliminary evidence]: Anti-inflammatory for various conditions; explored for COVID-19

Mechanism of Action

Active Compounds

Immunomodulatory Mechanisms

1. NF-kB pathway inhibition: Andrographolide directly inhibits NF-kB activation, reducing production of pro-inflammatory mediators. This is the best-characterized mechanism. [Source: PMC3619690]
2. COX-2 and iNOS suppression: Inhibition of cyclooxygenase-2 expression and inducible nitric oxide synthase, reducing inflammation. [Source: Overview of pharmacological activities, Pubmed 30040451]
3. Cytokine modulation: Modulation of TNF-alpha, IL-1beta, IL-6 production
4. T-cell and NK cell activation: Enhancement of cytotoxic T-lymphocyte and NK cell activity at therapeutic doses
5. Direct antiviral activity: In vitro evidence for interference with viral docking and replication mechanisms [UNCERTAIN — clinical relevance not established]
6. Antipyretic activity: Demonstrated in animal models, relevant to clinical fever reduction

Kan Jang Synergy

The Kan Jang formulation combines Andrographis paniculata extract (SHA-10) with Eleutherococcus senticosus extract (SHE-3). The rationale is that Andrographis provides direct anti-inflammatory and antiviral effects while Eleuthero provides adaptogenic support and immune enhancement. Panossian et al. demonstrated that the combination affects immune activation markers, lymphocyte proliferation, and cytokine production differently than either component alone. [Source: Pubmed 12487323]

Clinical Evidence Summary

Systematic Review and Meta-Analysis (Hu et al., 2017)

• 33 RCTs included in systematic review
• Andrographis alone or in combination was superior to placebo for reducing severity of URTI symptoms
• Specific symptom relief: sore throat (OR 2.3, 95% CI 1.69-3.14), tiredness (OR 1.28, 95% CI 1.07-1.53), sleeplessness (OR 1.71, 95% CI 1.38-2.11)
• [Source: PLOS One, DOI: 10.1371/journal.pone.0181780]

Key Individual Trials

Evidence Quality Assessment

• Studies are generally well-designed (double-blind, placebo-controlled, adequate sample sizes)
• The Kan Jang studies were primarily conducted by the same research group (Panossian, Melchior, Caceres) with manufacturer involvement, which is a potential bias concern
• Independent replication of key findings is limited [NEEDS-RESEARCH]
• Effect sizes are clinically meaningful (1-2 days shorter illness; significant symptom reduction)

European vs. US/Anglophone Consensus

Safety Profile

Contraindications

• Allergy to Acanthaceae family: Known allergy is an absolute contraindication
• Pregnancy: Strictly contraindicated. Animal studies show anti-fertility effects (reduced spermatogenesis, potential abortifacient properties at high doses). No human safety data for pregnancy. [Source: TGA Safety Review]
• Autoimmune disease: Theoretical concern due to immunomodulatory effects [UNCERTAIN]
• Bleeding disorders: Andrographolide has antiplatelet activity; caution with coagulopathies

Drug Interactions

• Anticoagulants/antiplatelet agents: Additive bleeding risk due to antiplatelet effects of andrographolide
• Antihypertensives: Andrographolide may lower blood pressure; additive hypotension possible
• Immunosuppressants: Theoretical antagonism
• CYP interactions: Limited data; no major CYP interactions identified clinically [NEEDS-RESEARCH]
• Overall: Drug interaction risk is LOW-MODERATE

Side Effects

• Gastrointestinal: Nausea, vomiting, diarrhea, abdominal discomfort (dose-dependent)
• Taste disturbance: Bitter/metallic taste (common, reflects the “King of Bitters” name)
• Headache and fatigue: Reported in some trials
• Pruritus and rash: Uncommon
• Anaphylaxis/allergic reactions: Rare but documented. Australia’s TGA issued a safety review noting anaphylactic reactions. Methanol-based extracts may increase allergy risk. [Source: TGA safety review]
• Pooled incidence of serious adverse events: 0.02 per 1,000 patients in meta-analysis (95% CI 0.0-0.5) [Source: Pubmed 33372366]

Pregnancy/Lactation

• Pregnancy: CONTRAINDICATED. Animal studies show anti-implantation and anti-fertility effects. Insufficient human data but precautionary principle applies.
• Lactation: Insufficient data. Not recommended.

Clinical Dosage

Kan Jang (Fixed Combination)

• Composition: Andrographis paniculata extract (SHA-10) + Eleutherococcus senticosus extract (SHE-3)
• Dosage: 6 tablets daily (providing 60-90 mg andrographolides per day)
• Duration: 3-5 days for URTI; up to 14 days for COVID-19 in clinical trials

Andrographis Monotherapy

• Standardized extract: Typically standardized to 10-30% andrographolides
• Clinical dose: 1,200 mg Andrographis extract daily (divided doses), providing approximately 60 mg andrographolides
• Dried leaf/herb: 3-6 g daily (traditional dose)
• Duration: 5-7 days for acute URTI (start at first symptoms)

Key Commercial Products

• Kan Jang (Swedish Herbal Institute/Bittner): Most-studied product; fixed combination
• Andrographis AP-Bio (MediHerb): Standardized extract
• ParActin (HP Ingredients): Standardized to 30% andrographolides (primarily for anti-inflammatory indication)

Sources

• HMPC Assessment Report: Andrographis paniculata Nees, folium (EMA/HMPC/320433/2012)
• Hu XY et al. “Andrographis paniculata for symptomatic relief of acute respiratory tract infections: A systematic review and meta-analysis.” PLOS One. 2017;12(8):e0181780.
• Gabrielian ES et al. “A double blind, placebo-controlled study of Andrographis paniculata fixed combination Kan Jang in the treatment of acute upper respiratory tract infections including sinusitis.” Phytomedicine. 2002;9(7):589-597. (Pubmed 12487322)
• Panossian A et al. “Effect of andrographolide and Kan Jang on proliferation of human lymphocytes, production of cytokines and immune activation markers.” Phytomedicine. 2002;9(7):598-605. (Pubmed 12487323)
• Caceres DD et al. “Use of visual analogue scale measurements to assess the effectiveness of Andrographis paniculata.” Phytomedicine. 1999;6(3):163-171.
• TGA Safety Review: Safety review of Andrographis paniculata and anaphylactic/allergic reactions. (tga.gov.au)
• Jayakumar T et al. “Experimental and Clinical Pharmacology of Andrographis paniculata and Its Major Bioactive Phytoconstituent Andrographolide.” Evid Based Complement Alternat Med. 2013;2013:846740. (PMC3619690)
• Panossian A et al. “Efficacy of Kan Jang in Patients with Mild COVID-19.” Pharmaceuticals. 2023;16(9):1196. (PMC10535596)

Connections

• Eleuthero: Component of Kan Jang combination; shared research group (Panossian)
• Echinacea: Comparable indication (URTI) but different mechanism; sometimes marketed as “Indian Echinacea”
• Pelargonium: Both are non-European traditional herbs that have gained European clinical evidence