Andrographis Paniculata

1. What conditions has Andrographis Paniculata been studied for?

• HIV infection (phase I safety/tolerability; immune markers): Andrographolide (a key constituent) studied in HIV-positive patients and healthy volunteers, with outcomes including CD4(+) counts and plasma HIV-1 RNA.

• Uncomplicated upper respiratory tract infection (URTI) / common cold: Multiple randomized, double-blind, placebo-controlled trials using Andrographis extracts (e.g., KalmCold 200 mg/day; SHA-10 1200 mg/day) assessing symptom scores (VAS) over ~5 days.

• Pharyngotonsillitis: Randomized, double-blind comparison of Andrographis (3 g/day or 6 g/day) vs paracetamol for 7 days, focusing on fever and sore throat relief.

• Rheumatoid arthritis (RA): Prospective, randomized, double-blind, placebo-controlled study of an extract (Paractin; 30% total andrographolides) for 14 weeks, assessing pain and joint outcomes plus labs (e.g., rheumatoid factor).

• Ulcerative colitis (UC): Randomized, double-blind trials of HMPL-004 in mild-to-moderate UC, including (a) comparison vs mesalazine and (b) placebo-controlled dose-ranging (1200 mg/day and 1800 mg/day) for 8 weeks.

2. Does it work in treating those conditions? Summarize the evidence.

• Common cold / URTI symptoms: Evidence from multiple placebo-controlled trials suggests symptom improvement.

  • KalmCold (200 mg/day, n=223): By day 5, symptom scores improved significantly vs placebo for all tracked symptoms except earache; overall symptom score reduction was significantly greater than placebo, and the study reports overall efficacy was ~2.1 times higher than placebo.

  • SHA-10 extract (1200 mg/day, n=158 completers): Significant symptom intensity reductions vs placebo began by day 2 for several symptoms (e.g., tiredness, sleeplessness, sore throat, nasal secretion), and by day 4 there was a significant decrease in intensity of all symptoms in the Andrographis group.

  Interpretation: Across these trials, Andrographis extracts appear to reduce common cold/URTI symptom severity over several days, with effects emerging as early as day 2 in one study.

• Pharyngotonsillitis: Mixed/limited evidence.

  • 3 g/day vs 6 g/day vs paracetamol (n=152): At day 3, paracetamol and high-dose Andrographis (6 g/day) were significantly more effective than low-dose (3 g/day) for fever and sore throat relief; by day 7, clinical effects were not different among groups.

  Interpretation: Higher-dose Andrographis may provide earlier symptom relief comparable to paracetamol, but differences did not persist to day 7.

• Ulcerative colitis (mild-to-moderate): Evidence suggests possible benefit, particularly at higher dose, though results vary by endpoint.

  • HMPL-004 1200 mg/day vs mesalazine 4500 mg/day (n=120): Clinical remission/response were 21%/76% with HMPL-004 vs 16%/82% with mesalazine; colonoscopy remission/response were 28%/74% vs 24%/71%. No significant differences between groups, suggesting similar efficacy in this study.

  • Placebo-controlled (n=224): Clinical response at week 8 was 45% (1200 mg), 60% (1800 mg), vs 40% placebo; only the 1800 mg dose was statistically superior to placebo (P=0.0183). Clinical remission rates (34–38% vs 25% placebo) were not statistically significant in this abstract.

  Interpretation: HMPL-004 at 1800 mg/day improved clinical response vs placebo; remission benefits are less certain based on the reported statistics.

• Rheumatoid arthritis: Suggestive but not definitive evidence.

  • Paractin (30% andrographolides) for 14 weeks (n=60): Pain decreased vs placebo but not significantly. However, multiple within-group improvements were reported in tender/swollen joint measures, HAQ, and SF-36, and reductions in rheumatoid factor, IgA, and C4 were noted.

  Interpretation: Signals of benefit exist, but the abstract emphasizes the need for a larger and longer trial; the primary pain outcome was not statistically significant vs placebo.

• HIV (immune markers/viral load): Not established as an antiviral treatment; limited evidence of immune marker change with safety concerns.

  • Phase I andrographolide dose-escalation: At 10 mg/kg, mean CD4(+) rose from 405 to 501 cells/mm(3) (p=0.002), but there were no statistically significant changes in plasma HIV-1 RNA. Trial was interrupted at 6 weeks due to adverse events including an anaphylactic reaction.

  Interpretation: Possible CD4(+) increase was observed without viral load reduction; clinical relevance is uncertain and safety/tolerability limited escalation.

3. What health benefits does it have?

• Symptom relief in uncomplicated common cold/URTI: Reduced severity and/or prevalence of symptoms such as sore throat, nasal secretion, tiredness, sleeplessness, cough-related measures, and overall symptom scores in placebo-controlled trials (effects noted by day 2 and clearer by day 4–5 in the cited studies).

• Potential earlier relief of fever and sore throat in pharyngotonsillitis (higher dose): High-dose Andrographis (6 g/day) performed similarly to paracetamol at day 3 for fever and sore throat relief, though differences were not present by day 7.

• Anti-inflammatory/immune-modulating effects relevant to inflammatory disease: UC trials show comparable outcomes to mesalazine in one study and improved clinical response vs placebo at 1800 mg/day in another, consistent with the abstract’s mechanistic note that extracts inhibit inflammatory mediators (TNF-α, IL-1β, NF-κB).

• Possible adjunctive benefit in rheumatoid arthritis: Improvements in joint tenderness/swelling indices and function/quality-of-life measures were reported within the active group, with associated reductions in rheumatoid factor and some immune markers; however, confirmatory evidence is limited.

• Possible increase in CD4(+) counts in HIV (not antiviral efficacy): A phase I trial observed a statistically significant CD4(+) rise at 10 mg/kg andrographolide, without significant HIV RNA changes.

4. Does it have any downsides or side effects?

• Risk of allergic reaction (including severe): In the phase I andrographolide trial in HIV-positive patients/healthy volunteers, the study was interrupted at 6 weeks due to adverse events including an anaphylactic reaction in one patient; adverse events resolved by end of observation.

• Minor side effects reported in respiratory infection/pharyngotonsillitis studies:

  • KalmCold URTI trial: “Only a few minor adverse effects” with no significant difference vs placebo.

  • Pharyngotonsillitis trial: Minimal, self-limiting side effects occurred in about 20% in each group (including paracetamol), suggesting tolerability similar to comparator in that study.

  • SHA-10 common cold trial: No adverse effects were observed or reported in the abstract.

• Adverse events in ulcerative colitis trials were common but similar to placebo: In the placebo-controlled UC trial, adverse events occurred in 60% (1200 mg), 53% (1800 mg), and 60% (placebo), suggesting no clear excess overall—though the abstract does not detail event types.

• Limitations of the safety evidence: Several studies are short (e.g., 5–8 weeks or less), and abstracts often do not specify adverse event types; rare but serious reactions (e.g., anaphylaxis) may not be well captured in small trials.

5. Is it beneficial or harmful for any genetic variations (pharmacogenomics)?

The provided abstracts do not report pharmacogenomic analyses (e.g., outcomes stratified by genotype) and do not identify specific genetic variants that predict benefit or harm from Andrographis paniculata or andrographolide.

• What can be said from these abstracts: No genotype-dependent dosing, efficacy, or adverse event signals are described.

• Practical implication: Based on these abstracts alone, there is insufficient evidence to recommend Andrographis specifically for—or to avoid it in—people with particular genetic variants.

References

1. A phase I trial of andrographolide in HIV positive patients and normal volunteers
   C Calabrese, S H Berman, J G Babish, X Ma, L Shinto (2000)
2. A randomized double blind placebo controlled clinical evaluation of extract of Andrographis paniculata (KalmCold) in patients with uncomplicated upper respiratory tract infection
   R C Saxena, R Singh, P Kumar, S C Yadav, M P S Negi (2010)
3. Efficacy of Andrographis paniculata, Nees for pharyngotonsillitis in adults
   V Thamlikitkul, T Dechatiwongse, S Theerapong, C Chantrakul, P Boonroj (1991)
4. Use of visual analogue scale measurements (VAS) to asses the effectiveness of standardized Andrographis paniculata extract SHA-10 in reducing the symptoms of common cold. A randomized double blind-placebo study
   D D Cáceres, J L Hancke, R A Burgos, F Sandberg, G K Wikman (1999)
5. Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo-controlled trial
   R A Burgos, J L Hancke, J C Bertoglio, V Aguirre, S Arriagada (2009)
6. Randomised clinical trial: herbal extract HMPL-004 in active ulcerative colitis - a double-blind comparison with sustained release mesalazine
   T Tang, S R Targan, Z-S Li, C Xu, V S Byers (2011)
7. Andrographis paniculata extract (HMPL-004) for active ulcerative colitis
   William J Sandborn, Stephan R Targan, Vera S Byers, Dean A Rutty, Hua Mu (2013)