Could andrographolide from Andrographis paniculata help with multiple sclerosis?

Relation

Ciampi E, Uribe-San-Martin R, Carcamo C, et al. Efficacy of Andrographolide in Non-Active Progressive Multiple Sclerosis: A Prospective, Exploratory, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study.BMC Neurol. 2020;20(1):1-10.

Study objective

To determine whether a pure andrographolide compound (AP) has been extractedAndrographis paniculatacould reduce brain atrophy and disability progression in non-active progressive multiple sclerosis

Draft

A 24-month, double-blind, placebo-controlled, single-site randomized trial in Chile

intervention

The andrographolide group received andrographolide (99.5% purity) 140 mg orally twice daily for 24 months. The placebo group received an identical control.

Participant

There were 44 patients (24 women, 20 men) who were randomized to this study and 37 (24 women, 13 men) participants who completed the study. Of the 37 participants, 17 were in the placebo group and 20 were in the AP group.

All patients were older than 18 years (mean = 58 years old for the placebo group and 59 years old for the AP group) and had a diagnosis of non-active, primary or secondary, progressive MS according to the criteria of McDonald 2010. They had no evidence of relapse or new brain lesions in the past year. All patients had a baseline Expanded Disability Status Scale (EDSS) score of less than 8.0 and a Mini Mental State Exam (MMSE) score of more than 24.

Exclusion criteria included patients with relapsing-remitting MS or active (clinical or radiological) progressive MS, use of glucocorticoids for 3 months before the study or immunomodulatory medications for 6 months before the study, uncontrolled medical or psychiatric illnesses, and pregnancy or inability to use contraception.

Study parameters assessed

Clinical disability was assessed every 12 weeks for 96 weeks by a blinded investigator who tracked scores on the EDSS and the Multiple Sclerosis Functional Composite (MSFC).

Whole-brain MRI was performed at baseline and 24 months. Retinal fiber nerve layer thickness was estimated at baseline and 24 months.

This study evaluated changes in disability progression. To quantify this, various measures have been used including:

• Mittlere Änderung der retinalen Nervenfaserschichtdicke gemessen mit optischer Kohärenztomographie (OTC)
• Mittlere Veränderung in einem zeitgesteuerten 25-Fuß-Gehtest (T25WT), einem 9-Loch-Peg-Test (9HPT), dem Symbol Digit Modalities Test (SDMT), der Fatigue Severity Scale (FSS), der Multiple Sclerosis Impact Scale (MSIS29) und das Beck-Depressions-Inventar (BDI)

Primary outcome measures

The primary endpoint was the difference in mean percent change in brain volume (mPBVC) measured by MRI at baseline and 2 years.

Key insights

Although the primary outcome measure of percent change in brain volume did not reach statistical significance, two other secondary outcome measures reached statistical significance. A significant reduction in brain atrophy was found in the AP group compared to the placebo group (36.5% measured with SIENA and 75% post hoc measured with BPF,P=0.033). The percentage of patients with 12-week confirmed disability progression also showed a statistically significant decrease in the AP group compared to the placebo group (HR = 0.596; 95% CI: 0.2000-1.777).

Practice implications

Andrographis paniculatais traditionally used to treat inflammation and bacterial infections. The most active component is believed to be andrographolide, a diterpenoid. Andrographolide has been found to have anti-obesity, anti-cancer, anti-diabetic, and anti-inflammatory effects, to name a few.¹Clinically, I have observed that persistent Lyme disease and co-infections present as a complex constellation of symptoms associated with unchecked inflammatory pathways. In my practice, tinctures are made from the above-ground partsAndrograpis paniculata(usually along with other plants) have been a valuable player in the fight against the inflammation caused by Lyme disease. Given my history with this plant, I was not surprised that the suspected active ingredient could improve symptoms and slow the progression of MS.

In my experience, there is significant overlap between tick-borne diseases and MS. I have seen several patients diagnosed with MS who had significant improvement in their MS symptoms when an underlying tick-borne disease was treated. Was the MS made worse by the tick-borne disease? Did tick-borne disease cause MS? Was MS actually a misdiagnosis? It's anyone's guess. Unabhängig davon empfehle ich, Ihre MS-Patienten auf durch Zecken übertragene Krankheiten zu untersuchen. You may be quite surprised by what you find.

In the context of MS, it would be interesting to see whether high doses of the whole plant, as a tincture or as a hot water extract, would have similar beneficial effects to andrographolide

Ich benutze Andrographis paniculataas a tincture to treat tick infections for many years in my practice. I started this at the recommendation of noted herbalist Stephen Harold Buhner. Buhner has written extensively about this plant and explains that it is a good systemic herb that can cross the blood-brain barrier and reach places where bacteria hide.²I have since found these properties to be very important in the case of Lyme diseaseBorellia Spirochetes are notorious for hiding in various body spaces.

The authors of the current study stated that AP was well tolerated and was shown to have mild potential side effects (rash and dysgeusia). Clinically, this would be a welcome relief given the potential side effects of anti-inflammatory and immunomodulatory drugs currently used to treat MS.

The authors of a study in theNew England Journal of Medicinestudied the side effects of ocrelizumab (a monoclonal antibody used to treat MS) in a study known as the OPERA I trial. In this study, 80.1% of 408 patients noted an adverse event. Serious adverse events were reported in 6.9% of patients. Serious adverse events included infections and neoplasms.³

In the current study, 13% of patients in the AP group and 42.8% of patients in the placebo group reported a “severe” adverse event. This was due to more cardiovascular events in the placebo group despite balanced comorbidities at baseline. Reported adverse events consisted of skin rashes (12/23 in the AP group vs. 0/21 in the placebo group) and taste disturbances (3/23 in the AP group vs. 0/21 in the placebo group). So almost half of the AP group got rashes. Apparently, in most cases, the rashes were not bad enough to be reported as “severe” adverse events. Only one person dropped out of the AP group, and that was due to dysgeusia.

In clinical practice, if half of the people I treat with a particular therapy develop a rash, this would definitely deter them from continuing treatment. Given current treatment options for MS, a small rash may not be such a serious side effect to tolerate. In the current study, the rashes did not appear to deter anyone in the treatment group from continuing treatment. Fewer people in the treatment group dropped out of the study (13%) than in the placebo group (19%).

Buhner noted that there are reports of allergic reactions to AP. For those who experience side effects from this plant, skin reactions are the most commonly observed manifestation. No deaths from allergic reactions to this plant have been reported in the literature.⁴Personally, I have not seen many rashes from using AP tincture and I have used it on several hundred patients. Whether this response is dose dependent or other confounders are involved is not clear.

In the context of MS, it would be interesting to see whether high doses of the whole plant, as a tincture or as a hot water extract, would have similar beneficial effects to andrographolide, as the increased occurrence of skin rashes with pure andrographolide may prevent some from following through with treatment.

Now that there is interest in pure andrographolide extract, there will likely be drug development focused on this phytochemical. Plants are a ubiquitous source of inspiration for drug development. In the 30 years up to 2012, up to 50% of all new drugs were at least partially derived from plant molecules. Some of the more recently developed plant-derived medicines include artemetherArtemesia anuafor the treatment of malaria, nitisinoneCallistemon citrinusfor the treatment of tyrosinemia and galantamineGalanthus nivalisused to treat Alzheimer's disease.⁵

It is interesting that andrographolide has anticancer and anti-infectious properties, while ocrelizumab increases the risk of cancer and infections in some cases.³

restrictions

The current study was a very small study. Perhaps future studies will confirm that andrographolide is a useful agent in the treatment of MS. Andrographolide may also reduce the risk of cancer and infections in people who use it to treat MS and other diseases. Part of the beauty of botanical medicine is that you can target multiple biological processes with one plant or plant extract.