A Unique Andrographis Extract for Multiple Sclerosis
Andrographis Extract
Estimates indicate1 that about 2.8 million people worldwide suffer from multiple sclerosis (MS), a potentially disabling autoimmune disease in which the immune system attacks the protective sheath (myelin) that covers nerve fibers and causes communication problems between your brain and the rest of your body. Eventually, MS can cause permanent damage or deterioration of the nerves and, depending on the amount of nerve damage and which nerves are affected, may result in a variety of different symptoms including losing the ability to walk independently or at all—although others with MS may experience long periods of remission without any new symptoms.2 Although there’s currently no cure for MS, medical treatment can help speed recovery from attacks, as well as modify the course of the disease and manage symptoms. It turns out that the herb Andrographis paniculata can also help in the management of MS. That is the subject of this article.
Symptoms of MS
Before jumping into a discussion on Andrographis paniculata, let’s first discuss some of the symptoms of this disease. Fatigue is the most common symptom of MS, occurring 75–95 percent of patients.3 Although the exact cause of MS-related fatigue is not known, some evidence suggests that immunological factors, such as elevated levels of proinflammatory cytokines, may contribute to subjective fatigue in MS patients4–and a large number of clinical studies have shown increased pro-inflammatory cytokines in the blood and cerebrospinal fluid of patients with MS.5
Additional symptoms that may be experienced by an MS patient include numbness or weakness in one or more limbs that typically occurs on one side of your body at a time, or your legs and trunk, electric-shock sensations that occur with certain neck movements, especially bending the neck forward, tremor, lack of coordination or unsteady gait, partial or complete loss of vision, usually in one eye at a time, blurry vision, slurred speech, dizziness and problems with sexual, bowel and bladder function.6
Andrographis paniculata Background
Andrographis paniculata is an herb with a history of use in both ayurvedic and traditional Chinese medicine. Called the “king of bitters” in Asia, Andrographis contains a number of bitter constituents which appear to have both immune-modulating and anti-inflammatory activity.7 Specifically, during the screening of a plant extract library of traditional Chinese herbal medicines, researchers found that NF-kB activity was potently inhibited by andrographolide, an abundant component of the plant Andrographis.8 Subsequent research verified this effect, and further demonstrated that andrographolide also reduced the expression of other proinflammatory proteins, such as COX-29 and cytokines.10-11 In fact, a recent article in the scientific journal Biochemical Pharmacology, suggested that “andrographolide and its analogs have great potential to be the next new class of anti-inflammatory agents …”12
Andrographolide/Andrographis in Animal Research
Alloydina is a type of neuropathic pain, defined as “pain due to a stimulus that does not normally provoke pain.” For example, from brushing your hair or pulling bed covers over you, feels unpleasant or painful. Unfortunately, MS nerve damage in the brain and spinal cord can result in allodynia.13 In conventional medicine, treatment options that could reduce the pain from allodynia include opioids, ion channel blockers, anticonvulsants, antidepressants, topical treatments (lidocaine patch, capsaicin), ketamine and NSAIDS (non-steroidal anti-inflammatory drugs) for acute flares of pain. However, according to Wang et al., “some of the treatments have been outweighed by their side effects, and relief from pain is still not available for about 10 percent of patients.” Andrographolide may be able to help. In animal research,14 mice with nerve damage who were treated with androgapholide had reduced mechanical allodynia more than treatment with NSAIDS at the same concentration. Furthermore, the observed behavior was associated with a reduction in inflammatory cytokine produced in the spinal cord, further verifying the efficacy of andrographolide for this purpose. This suggests that androgapholide may also have value in allodynia in MS.
Other types of pain and inflammation may be caused by serum pro-inflammatory cytokines, such as IL-1β, IL-6 and TNF-α, as well as the concentration of matrix metalloproteinases, including MMP-1, MMP-3, MMP-8 and MMP-13. In other animal research,15 Andrographis paniculata extract providing 50 percent total andrographolides (ParActin, HP Ingredients) was shown to decrease these markers and substantially reverse the loss of hind limb weight-bearing and the cartilage damage resulting from osteoarthritis in rats. Since many of these same markers are elevated in MS, this andrographolide source may also help with MS pain and inflammation as well.
Voltage-gated calcium channels (VGCCs) play a critical role in neuroinflammatory diseases, such as MS,16 so selectively blocking VGCCS holds promise for reduced pain in MS and other such conditions. Consequently, the possible blockade of VGCCs by Andrographis paniculata dried extract in vas deferens smooth muscle was investigated in rats.17 The results were Andrographis extract was shown to selectively block VGCCs. This may reduce the potential firing frequency of pain sensation in neurons.
The process of uncontrolled internal scarring, called fibrosis, is now emerging as a pathological feature shared by both peripheral and central nervous system diseases, including MS. The scientific literature specifically describes the formation of a fibrotic scar near the well-known glial scar in MS patients which contributes to the impairment of the remyelination process.18 A study19 was conducted in an animal model of Duchenne muscular dystrophy, suggesting that andrographolide may help with fibrosis. Mice were treated with andrographolide for three months. The results were that the mice exhibited less severe muscular dystrophy than untreated dystrophic mice. They also performed better in an exercise endurance test and had improved muscle strength in isolated muscles, reduced skeletal muscle impairment, diminished fibrosis and a significant reduction in TGF-β signaling, which would otherwise exacerbate the inflammatory response and aggravates the fibrotic response. Consequently, it is possible that andrographolide may reduce disability in MS by reducing muscle tearing and fibrosis, thereby improving muscle strength.
Prior Research on a Standardized Andrographis paniculata Extract in Humans
In the January 2018 issue of Vitamin Retailer, I wrote an article called “Standardized Andrographis paniculata for Pain & Inflammation.” In it I described human clinical research from 2009 and 2013 showing that Andrographis paniculata extract providing 50 percent total andrographolides (ParActin, HP Ingredients) was effective in treating rheumatoid arthritis (an autoimmune disease).20,21 Given that Andrographis paniculata has been shown to reduce proinflammatory proteins, this benefit makes sense. Given that this article is about the effect of Andrographis in the treatment of MS, It’s also interesting that a standardized Andrographis extract was effective in the treatment of another autoimmune inflammatory disorder.
Research on a Standardized Andrographis paniculata Extract and MS
Since fatigue is rated as one of the most common and disabling symptoms in MS, a 12-month randomized, double-blind, placebo-controlled trial22 was conducted assessing the effects of 340 mg/day of a standardized Andrographis extract (NeuroActin, HP Ingredients), on relapse rate and fatigue in 22 relapsing-remitting MS (RRMS) patients receiving interferon beta. This assessment was done using the Fatigue Severity Scores (FSS). Results were that patients treated with Andrographis showed a significant 44 percent reduction in their FSS score as compared to the placebo. Researchers concluded that Andrographis was well tolerated in patients, and it significantly reduces fatigue in patients with RRMS receiving interferon beta in comparison to placebo and only interferon beta treatment.
There is a progressive phase of MS that appears to have significant neurodegenerative mechanisms. The classification of progressive MS (PMS) has been re-organized into categories of active vs. not active inflammatory disease and the presence vs. absence of gradual disease progression. Clinical trial experience to date in PMS with anti-inflammatory medications has shown limited effect. Andrographolide is an anti-inflammatory agent, that has been proposed as a potential drug for autoimmune disorders, including MS. The present 24-month clinical trial23 explored the efficacy and safety of andrographolide (AP, as NeuroActin, HP Ingredients) compared to placebo in 44 patients with not active primary or secondary progressive MS. The primary efficacy endpoint was the mean percentage brain volume change (mPBVC). Secondary efficacy endpoints included three-month confirmed disability progression (3-CDP) and mean Expanded Disability Status Scale (EDSS) change. The results were that annualized mPBVC was – 0.679 percent for the AP group and – 1.069 percent for the placebo group. In the AP group, 30 percent had 3-CDP compared to 41 percent in the placebo group. The average EDSS change was – 0.025 in the AP group and + 0.352 in the placebo group (p = 0.042). In conclusion, AP was well tolerated and showed a potential effect in reducing brain atrophy and disability progression, that need to be further evaluated in a larger clinical trial.
Andrographis paniculata Patents for MS
The research on Andrographis was sufficiently compelling and novel that a U.S. patent (8,084,495 B2) was awarded entitled “Composition of labdane diterpenes extracted from andrographis paniculata, useful for the treatment of autoimmune diseases, and Alzheimer disease by activation for PPR-gamma receptors.” The patent indicated that Andrographis compounds “inhibits the synthesis of pro-inflammatory cytokines, activates the PPAR-gamma receptor and diminishes nuclear factor kappa B. The compound is useful to treat auto-immune diseases … ” This patent was awarded to Herbal Powers, aka, HP Ingredients. Subsequently, another patent was awarded, entitled, “Combination therapy with interferon and andrographolides for multiple sclerosis.” This patent indicated that the effectiveness of interferon for treating MS and other demyelinating diseases is synergistically potentiated when andrographolides is used at the same time.
Conclusion
MS is a potentially disabling autoimmune disease for which there’s currently no cure—although medical treatment can help speed recovery from attacks, as well as modify the course of the disease and manage symptoms. Likewise, a unique extract of the herb Andrographis paniculata (NeuroActin, HP Ingredients) has been shown to significantly reduce fatigue (the most common symptom of MS) in patients with relapsing-remitting MS. This same Andrographis extract was also shown to help reduce the loss of brain volume as well as mitigate disability progression scores associated with MS. Additionally, patents have been awarded for the use of this Andrographis extract in treating autoimmune diseases and potentiating interferon treatment for MS when taken at the same time.
References:
1 Walton C, King R, Rechtman L, et al. Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition. Mult Scler. 2020 Dec; 26(14): 1816–1821.
2 Tobin O. Multiple sclerosis. Mayo Clinic. January 7, 2022. Retrieved July 11, 2022 from www.mayoclinic.org/diseases-conditions/multiple-sclerosis/symptoms-causes/syc-20350269.
3 Multiple Sclerosis: Fatigue. Cleaveland Clinic. Last reviewed by a Cleveland Clinic medical professional on January 28, 2019. Retrieved July 11, 2022 from https://my.clevelandclinic.org/health/diseases/14136-multiple-sclerosis-fatigue.
4 Hanken K, Eling P, Hildebrandt H. The representation of inflammatory signals in the brain – a model for subjective fatigue in multiple sclerosis. Front Neurol. 2014;5:264.
5 Bai Z, Chen D, Wang L, et al. Cerebrospinal Fluid and Blood Cytokines as Biomarkers for Multiple Sclerosis: A Systematic Review and Meta-Analysis of 226 Studies With 13,526 Multiple Sclerosis Patients. Front Neurosci. 2019 Oct 4;13:1026.
6 Tobin O. Multiple sclerosis. Mayo Clinic. January 7, 2022. Retrieved July 11, 2022 from www.mayoclinic.org/diseases-conditions/multiple-sclerosis/symptoms-causes/syc-20350269.
7 Bone K. Clinical Applications of Ayurvedic and Chinese Herbs: Monographs for the Western Herbal Practitioner. Queensland, Australia: Phytotherapy Press; 1996:96–100.
8 Xia YF, Ye BQ, Li YD, Wang JG, He XJ, Lin X, Yao X, Ma D, Slungaard A, Hebbel RP, Key NS, Geng JG. Andrographolide attenuates inflammation by inhibition of NF-kappa B activation through covalent modification of reduced cysteine 62 of p50. J Immunol. 2004 Sep 15;173(6):4207-17.
9 Hidalgo MA, Romero A, Figueroa J, Cortés P, Concha II, Hancke JL, Burgos RA. Andrographolide interferes with binding of nuclear factor-kappaB to DNA in HL-60-derived neutrophilic cells. Br J Pharmacol. 2005 Mar;144(5):680-6.
10 Carretta MD, Alarcon P, Jara E, Solis L, Hancke JL, Concha II, Hidalgo MA, Burgos RA. Andrographolide reduces IL-2 production in T-cells by interfering with NFAT and MAPK activation. Eur J Pharmacol. 2009;602(2–3):413–21.
11 Burgos RA, Seguel K, Perez M, Meneses A, Ortega M, Guarda MI, Loaiza A, Hancke JL. Andrographolide inhibits IFN-gamma and IL-2 cytokine production and protects against cell apoptosis. Planta Med. 2005;71(5):429–34.
12 Tan WSD, Liao W, Zhou S, Wong WSF. Is there a future for andrographolide to be an anti-inflammatory drug? Deciphering its major mechanisms of action. Biochem Pharmacol. 2017 Sep 1;139:71-81.
13 Murphy KL, Bethea JR, Fischer R. Chapter 4: Neuropathic Pain in Multiple Sclerosis—Current Therapeutic Intervention and Future Treatment Perspectives. In Zagon IS, McLaughlin PJ. Multiple Sclerosis: Perspectives in Treatment and Pathogenesis. Brisbane (AU): Codon Publications; 2017.
14 Wang H-C, Tsay H-S, Shih H-N, et al. Andrographolide relieved pathological pain generated by spared nerve injury model in mice. Pharm Biol. 2018 Dec;56(1):124-131.
15 Lee D, Baek CY, Hwang JH, Kim M-Y. Andrographis paniculata Extract Relieves Pain and Inflammation in Monosodium Iodoacetate-Induced Osteoarthritis and Acetic Acid-Induced Writhing in Animal Models. Processes 2020; 8: 873.
16 Silva RBM, Greggio S, Venturin GT, et al. Beneficial Effects of the Calcium Channel Blocker CTK 01512-2 in a Mouse Model of Multiple Sclerosis. Mol Neurobiol. 2018 Dec;55(12):9307-9327.
17 Burgos RA, Imilan M, Sánchez NS, Hancke JL. Andrographis paniculata (Nees) selectively blocks voltage-operated calcium channels in rat vas deferens. J Ethnopharmacol. 2000 Jul;71(1-2):115-21.
18 D’Ambrosi N, Apolloni S. Fibrotic Scar in Neurodegenerative Diseases. Front Immunol. 2020 Aug 14;11:1394.
19 Cabrera D, Gutiérrez J, Cabello-Verrugio C. Andrographolide attenuates skeletal muscle dystrophy in mdx mice and increases efficiency of cell therapy by reducing fibrosis. Skeletal Muscle. 2014; 4:6.
20 Burgos RA, Hancke JL, Bertoglio JC, Aguirre V, Arriagada S, Calvo M, Cáceres DD. 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.
21 Hidalgo MA, Hancke JL, Bertoglio JC, Burgos RA. Andrographolide a New Potential Drug for the Long Term Treatment of Rheumatoid Arthritis Disease. In Matsuna H (ed). Innovative Rheumatology. Rijeka, Croatia: InTech; 2013:247–270.
22 Bertoglio JC, Baumgartner M, Palma R, et al. Andrographis paniculata decreases fatigue in patients with relapsing-remitting multiple sclerosis: a 12-month double-blind placebo-controlled pilot study. BMC Neurol. 2016 May 23;16:77.
23 Ciampi E, Uribe-San-Martin R, Cárcamo C. Efficacy of andrographolide in not active progressive multiple sclerosis: a prospective exploratory double-blind, parallel-group, randomized, placebo-controlled trial. BMC Neurol. 2020 May 7;20(1):173.
Gene Bruno, MS, MHS, the provost for Huntington University of Health Sciences, is a nutritionist, herbalist, writer and educator. For more than 40 years he has educated and trained natural product retailers and health care professionals, has researched and formulated natural products for dozens of dietary supplement companies, and has written articles on nutrition, herbal medicine, nutraceuticals and integrative health issues for trade, consumer magazines and peer-reviewed publications. He can be reached at gene.bruno@hchs.edu.
