Study Spotlight

Study Spotlight

Andrographis: the Next Big Thing for Pain Relief?


If you suffer from joint pain – whether due to wear and tear over time, or an autoimmune condition like rheumatoid arthritis – finding relief can be challenging.

However, an herb traditionally used in Ayurvedic practice (and elsewhere throughout Asia) may be next in line among strong joint supporting botanical ingredients like curcumin from turmeric or boswellia extract. That’s because like them, andrographis works through a number of different pathways in the body.

Laboratory research showed that andrographolide – a key compound from the botanical – inhibited cyclooxygenase-2 (COX-2) enzyme activity, relieving pain in much the same way as those other strong natural medicines.

This has borne out in human clinical work as well. For example, a placebo-controlled study of patients with rheumatoid arthritis found that andrographis reduced joint swelling and tenderness and, not surprisingly, reduced the inflammatory factors associated with the condition. While the researchers state that they would like to follow up with further study, these results are an excellent starting point.

And other scientific research has shown that andrographis stops inflammatory triggers that set off an overexpression of enzymes called matrix metalloproteinases or “MMPs” that would otherwise destroy cartilage between the joints. When MMPs are active at normal levels, they help keep cartilage and other joint structures supplied with fresh material, while pulling out the old. They are like bricklayers replacing mortar. But if too much mortar is removed – and not enough replaced, as is the case with many joint diseases, you run the risk of arthritis and a great deal of pain. Here again, the compound andrographolide appears to be the prime mover. It stops IL-1β inflammation and protects the healthy components of cartilage, including hyaluronic acid and collagen. While the authors of this study point to veterinary applications (having used equine cells), the work here has implications far beyond treating horses (although that is valuable, too.) It could signal a leap ahead for fighting joint destruction in humans as well.

Because andrographis fights inflammation and its damaging effects in so many ways, it is likely to be the next sought-after botanical for anyone dealing with pain. That makes it a much better choice than prescription or over-the-counter options that can cause potentially deadly damage to the liver and stomach lining or cause addiction in the pursuit of relief.

Abstracts:

Parichatikanond W, Suthisisang C, Dhepakson P, Herunsalee A. Study of anti-inflammatory activities of the pure compounds from Andrographis paniculata (burm.f.) Nees and their effects on gene expression. Int Immunopharmacol. 2010 Nov;10(11):1361-73.

In inflammation, the responses to noxious stimuli are controlled by the highly modulated interactions between various immune cells and chemical mediators. The purpose of this study is to evaluate and compare the anti-inflammatory effect of diterpenoids isolated from Andrographis paniculata, including dehydroandrographolide (AP1), andrographolide (AP2) and neoandrographolide (AP3), on the production of inflammatory cytokines and COX activities. Furthermore, the alteration of gene expression involved in this activity was investigated in the most potent compound to elucidate the other possible molecular mechanisms. AP1 (30.1 μM; 10 μg/ml) and AP2 (28.5 μM; 10 μg/ml) markedly inhibited COX-1 in ionophore A23187-induced human platelets. AP2 (28.5 μM) and AP3 (20.8 μM; 10 μg/ml) strongly suppressed the LPS-stimulated COX-2 activity in human blood. In addition, AP2 modulated the level of LPS-induced TNF-α, IL-6, IL-1β and IL-10 secretion in human blood in a concentration-dependent manner. The results revealed that AP2 exhibited the highest efficacy. Therefore, changes in the levels of mRNA transcripts by AP2 were further measured using human cDNA microarrays. The molecular response to AP2 was complex and mediated by various processes. Among the altered gene expressions, the genes involved in immune and inflammation processes were selectively down-regulated, such as cytokines and cytokine receptors (TNFSF14, TNF, TNFRSF6, and IL1A), chemokines (CCL8 and CXCL11), JAK/STAT signaling (JAK3 and STAT5A), TLRs family (TLR4 and TLR8) and NF-κB (NFKB1). Expression of some genes was validated using RT-PCR. The results demonstrated that AP1, AP2 and AP3 exhibited the anti-inflammatory effect by interfering COX and inflammatory cytokines and the underlying mechanisms of AP2 may be related to down-expression of genes involved in inflammatory cascade.

 

Burgos RA, Hancke JL, Bertoglio JC, et al. Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo-controlled trial. Clin Rheumatol. 2009 Aug;28(8):931-46.

Andrographis paniculata (Burm. f.) Wall ex Nees (Acanthaceae) possesses anti-inflammatory effects, attributed to the main constituent andrographolide proposed as alternative in the treatment of autoimmune disease. A prospective, randomized, double blind, and placebo-controlled study in patients with rheumatoid arthritis (RA) was performed. Tablets (Paractin) made of an extract of A. paniculata (30% total andrographolides) were administered three times a day for 14 weeks, after a 2-week washout period to 60 patients with active RA. The primary outcomes were pain intensity measured using a horizontal visual analog pain scale (VAPS). In addition, ACR, EULAR, and SF36 clinical parameters were recorded. The intensity of joint pain decreased in the active vs placebo group at the end of treatment, although these differences were not statistically significant. A significant diminishing for week in tender joint -0.13 95% confidence interval (CI; -0.22 to 0.06; p = 0.001), number of swollen joints -0.15 95%CI (-0.29 to -0.02; p = 0.02), total grade of swollen joint -0.27 95%CI (-0.48 to -0.07; p = 0.010), number of tender joints -0.25 95%CI (-0.48 to -0.02; p = 0.033), total grade of swollen joints -0.27 95%CI (-0.48 to -0.07; p = 0.01), total grade of tender joints -0.47 95%CI (-0.77 to -0.17; p = 0.002) and HAQ -0.52 95%CI (-0.82 to -0.21; p < 0.001) and SF36 0.02 95%CI (0.01 to 0.02; p < 0.001) health questionnaires was observed within the group with the active drug. Moreover, it was associated to a reduction of rheumatoid factor, IgA, and C4. These findings suggest that A. paniculata could be a useful "natural complement" in the treatment of AR; however, a larger trial and a more extended period of treatment is necessary in order to corroborate these results.

 

Tangyuenyong S, Viriyakhasem N, Peansukmanee S, Kongtawelert P, Ongchai S. Andrographolide Exerts Chondroprotective Activity in Equine Cartilage Explant and Suppresses Interleukin-1 β -Induced MMP-2 Expression in Equine Chondrocyte Culture. Int Sch Res Notices. 2014 Oct 29;2014:464136.

Cartilage erosion in degenerative joint diseases leads to lameness in affected horses. It has been reported that andrographolide from Andrographis paniculata inhibited cartilage matrix-degrading enzymes. This study aimed to explore whether this compound protects equine cartilage degradation in the explant culture model and to determine its effect on matrix metalloproteinase-2 (MMP-2) expression, a matrix-degrading enzyme, in equine chondrocyte culture. Equine articular cartilage explant culture was induced by 25 ng/mL interleukin-1β, a key inducer of cartilage degeneration, in cultures with or without andrographolide ranging from 10 to 50 μM. After 3-21 days, they were analyzed for the markers of cartilage degradation. It was found that interleukin-1β increased the release of sulfated glycosaminoglycans and hyaluronan from the explants into the culture media consistently with the decrease in uronic acid and collagen content in the cartilage explants. These catabolic effects were inhibited when cotreated with interleukin-1β and andrographolide. In primary equine chondrocytes, andrographolide suppressed interleukin-1β-induced MMP-2 mRNA expression and MMP-2 activity in the culture medium. These results confirmed the in vitro potent chondroprotective activities of this compound which were performed in cartilage explants and on a cellular level. These may indicate the application of andrographolide for therapeutic use in equine degenerative joint diseases.

Link to complete article: Andrographolide Exerts Chondroprotective Activity in Equine Cartilage Explant and Suppresses Interleukin-1β-Induced MMP-2 Expression in Equine Chondrocyte Culture

 

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