The released of the news in late December 2020 from Thailand’s health ministry on the approval of herbal medicine, Andrographis paniculata as an alternative treatment for Covid-19 has sparked the interest in the community. What is this natural magic bullet?
The southern Asian herb Andrographis paniculata
A new look at an old remedy
Andrographis paniculata is widely distributed and utilized in tropical and sub-tropical regions of Asia, including India, China, Thailand and Malaysia. Its use across this region is well known and have been documented in both traditional Chinese medicine (known as “Chuan Xin Lian” in Chinese) and Ayurveda system in India (known as Kalmegh in India). This medicinal plant is known as the “king of bitters” and because of the extremely bitter nature of the compounds, the plant is often taken in capsule form. Andrographis paniculata has been included in WHO monographs on selected medicinal plants and has very high efficacy in inhibiting influenza epidemic in India, 1919.
Andrographis paniculata can produce high quantities of biologically active diterpenoids and flavones, such as andrographolide, neoandrographolide that are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, virus infection, laryngitis and bacterial dysentery (1).
How it works?
The bioactive compound andrographolide can exert its inhibitory activity against pathogen-induced inflammation by binding to adenosine A receptor and induce nuclear factor (erthroid-derived 2)-like 2 (Nrf2) translocation, that subsequently inactivate GSK3β, leading to the upregulated expression of heme oxygenase 1 (HO-1) (2). Inflammation is part of the complicated biological response of body tissues to harmful stimuli such as pathogens, damaged cells or irritants, producing oxidative stress.
There are studies that reported that andrographolide could inhibit air inflammatory cell recruitment and lung injury by reducing protein and mRNA levels of pro-inflammatory cytokines in serum and bronchoalveolar lavage fluid by activating the MAPK and p65 signalling pathways. Besides that, Andrographis paniculata extracts were shown to inhibit secretion of RANTES, a key proinflammatory chemokine produced during viral infection, in an influenza infected bronchial epithelial cells model (3).
Andrographis and Covid-19
In late June 2020, phase I clinical trials on Andrographis for COVID-19 had begun at two hospitals in Thailand. Patients infected with COVID-19, having mild and moderate symptoms (fever and coughing) were included in the study. Six subjects received 60 mg of Andrographis (AP) extract capsules, while another 6 subjects received 100 mg AP extract, three times daily. This phase aimed to evaluate Andrographis on its’ safety, disinfecting activity and reducing virus-cell division. Results from the preliminary trial has showed that lower dose of Andrographis decreased cough volume and overall symptom severity within three days. Other symptoms significantly improved after 5 days, with real-time polymerase chain (PCR) test showing negative in two COVID-19 subjects. All six COVID-19 subjects’s PCR test reported to be negative after 3 weeks, however additional studies are needed to confirm the results (4).
Phase 2 clinical trials of the study began in September 2020 and 60 volunteers were divided into two groups: one receiving Andrographis and another one placebo. Further information on this study was not reported in detailed, but Thai government approved the used of Andrographis as a safe, effective, less costly Covid-19 treatment that has anti-inflammatory properties (5).
Subsequently, a group of researchers in Thailand also conducted high-content screening of Thai medicinal plants extracts and phytochemical compounds as anti-SARS-CoV-2 candidates. Among the investigated 122 crude extracts and purified compounds, Andrographis extract was found to exhibit inhibitory activities against SARS-CoV-2 in cell culture (6). Another in vitro study from Thailand has also shown the inhibition of SARS-CoV-2 by the 95% ethanol extract of Andrographis leaves in a human lung cell model (7).
It has been proposed that Andrographis could inhibit the virus entry and replication, as well as the expression or function of the mature proteins. Studies have shown that Andrographis targeted non-structural proteins of SARS-Cov-2 as the mechanism of action, by inhibiting the main protease activities of SARS-Cov-2. In addition, Andrographis was shown to have significant binding affinity towards the spike glycoproteins of SARS-CoV-2 and thus, inhibiting the viral entry into the host cells via ACE2 receptor (8).
“Mobilizing immune defenses as soon as symptoms arise is critically important for management of any upper respiratory infection.” -Roy Upton, the founder, president and editor of American Herbal Pharmacopoeia-
Herbal medicine has been used at the forefront battle against Covid-19 in China and treatment with herbs have been reported to have over 90% efficacy. It has been credited for the successful battle against COVID-19 in China.
In a nutshell, there is good reason for us to learn from ancient wisdom and accumulated clinical experience in combination with cutting edge science and technologies, to combat the COVID-19 pandemic and future diseases.
References:
1. Kanjanasirirat P, Suksatu A, Manopwisedjaroen S, Munyoo B, Tuchinda P, Jearawuttanakul K, Seemakhan S, Charoensutthivarakul S, Wongtrakoongate P, Rangkasenee N, Pitiporn S, Waranuch N, Chabang N, Khemawoot P, Sa-Ngiamsuntorn K, Pewkliang Y, Thongsri P, Chutipongtanate S, Hongeng S, Borwornpinyo S, Thitithanyanont A. High-content screening of Thai medicinal plants reveals Boesenbergia rotunda extract and its component Panduratin A as anti-SARS-CoV-2 agents. Sci Rep. 2020 Nov 17;10(1):19963. doi: 10.1038/s41598-020-77003-3. PMID: 33203926; PMCID: PMC7672115.
2. Mittal, S. P., et al. 2016. Andrographolide protects liver cells from H2O2 induced cell death by upregulation of Nrf-2/HO-1 mediated via adenosine A2a receptor signalling. Biochim Biophys Acta 1860(11 Pt A): 2377-2390. doi: 10.1016/j.bbagen.2016.07.005.
3. Zhu, T., et al. 2013. Andrographolide protects against LPS-induced acute lung injury by inactivation of NF-kappaB. PLoS One 8(2): e56407. doi: 10.1371/journal.pone.0056407
4. Two hospitals ready to trial traditional Thai medicine in treating Covid-19. The Nation Thailand June 28, 2020. Available at: www.nationthailand.com/news/30390444. Accessed January 27, 2021.
5. Trials underway to test efficacy of Andrographis paniculata extract for Covid-19. The Nation Thailand August 26, 2020. Available at: www.nationthailand.com/news/30393547. Accessed January 27, 2021.
6. Kanjanasirirat P, Suksatu A, Manopwisedjaroen S, Munyoo B, Tuchinda P, Jearawuttanakul K, Seemakhan S, Charoensutthivarakul S, Wongtrakoongate P, Rangkasenee N, Pitiporn S, Waranuch N, Chabang N, Khemawoot P, Sa-Ngiamsuntorn K, Pewkliang Y, Thongsri P, Chutipongtanate S, Hongeng S, Borwornpinyo S, Thitithanyanont A. High-content screening of Thai medicinal plants reveals Boesenbergia rotunda extract and its component Panduratin A as anti-SARS-CoV-2 agents. Sci Rep. 2020 Nov 17;10(1):19963. doi: 10.1038/s41598-020-77003-3. PMID: 33203926; PMCID: PMC7672115.
7. Kanjanasirirat P, Suksatu A, Manopwisedjaroen S, Munyoo B, Tuchinda P, Jearawuttanakul K, Seemakhan S, Charoensutthivarakul S, Wongtrakoongate P, Rangkasenee N, Pitiporn S, Waranuch N, Chabang N, Khemawoot P, Sa-Ngiamsuntorn K, Pewkliang Y, Thongsri P, Chutipongtanate S, Hongeng S, Borwornpinyo S, Thitithanyanont A. High-content screening of Thai medicinal plants reveals Boesenbergia rotunda extract and its component Panduratin A as anti-SARS-CoV-2 agents. Sci Rep. 2020 Nov 17;10(1):19963. doi: 10.1038/s41598-020-77003-3. PMID: 33203926; PMCID: PMC7672115.
8. Maurya, V. K.; Kumar, S.; Prasad, A. K.; Bhatt, M. L. B.; Saxena, S. K., Structure-based drug designing for potential antiviral activity of selected natural products from Ayurveda against SARS-CoV-2 spike glycoprotein and its cellular receptor. VirusDisease 2020, 31, (2), 179–193.