Andrographolide (1) is a labdane-type diterpene lactone and the major bioactive metabolite (2.39%) in the leaves of Andrographis paniculata (Acanthaceae). To further explore its stability, the thermal degradation kinetics of compound 1 at pH 2.0, pH 6.0, and pH 8.0 were modeled at three temperatures within 50-85 °C. The activation energy (Ea), shelf-life (t90%), and rate constant (k) for compound 1 were determined using the Arrhenius equation. Consequently, the results indicated that degradation followed first-order kinetics, and the optimum pH for stability was determined to be between pH 2.0 and 4.0. Major degradation products formed under pH 2.0 and pH 6.0 conditions were isolated and spectroscopically characterized by comparison with known compounds. Under pH 2.0 conditions, two degradation products were identified: isoandrographolide (2) and 8,9-didehydroandrographolide (3). Under pH 6.0 conditions, three degradation products were formed: 15-seco-andrographolide (4), 14-deoxy-15-methoxyandrographolide (5), and 11,14-dehydro-14-deoxyandrographolide (6). Anti-inflammatory and cytotoxicity assessments demonstrated reduced biological effects for the degradation products compared with compound 1. This highlights the importance of controlling pH during formulation to ensure product stability, sustained bioactivity, and patient benefit.

Center of Excellence in Marijuana Hemp and Kratom Walailak University Nakhon Si Thammarat 80160 Thailand

Centre for Natural Products Discovery School of Pharmacy and Biomolecular Sciences Liverpool John Moores University Byrom Street Liverpool L3 3AF UK

College of Pharmacy University of Florida Gainesville FL 32610 USA

Department of Pharmacognosy and Pharmaceutical Botany Faculty of Pharmaceutical Sciences Prince of Songkhla University Hat Yai Songkhla 90110 Thailand

Laboratory of Growth Regulators Palacký University and Institute of Experimental Botany The Czech Academy of Sciences Šlechtitelů 27 78371 Olomouc Czech Republic

Medicinal Plant Innovation Center of Mae Fah Luang University Mae Fah Luang University Chiang Rai 57100 Thailand

Natural Products Inc Evanston IL 60201 USA

Phytomedicine and Pharmaceutical Biotechnology Excellence Center Faculty of Pharmaceutical Sciences Prince of Songkhla University Hat Yai Songkhla 90110 Thailand

Pilot Plant Development and Training Institute King Mongkut's University of Technology Thonburi Bangkok 10150 Thailand

School of Allied Health Sciences Walailak University Nakhon Si Thammarat 80160 Thailand

School of Integrative Medicine Mae Fah Luang University Chiang Rai 57100 Thailand

See more in PubMed

National Drug Committee, National Essential Drug List Committee, Ministry of Public Health. Bangkok. (2016). https://www.chromeextension.com//efaidnbmnnnibpcajpcglclefindmkaj/https://ndi.fda.moph.go.th/uploads/file_news/202209301360287102.pdf

Bangkok Post. List of top herbs eyed for export. (2023). https://www.bangkokpost.com/thailand/general/2479664/list-of-top-herbs-eyed-for-export. Accessed on July 9, 2025.

Zhan, S. et al. Synthesis and evaluation of Andrographolide derivatives as potent anti-osteoporosis agents in vitro and in vivo. PubMed

Pholphana, N., Rangkadilok, N., Saehun, J., Ritruechai, S. & Satayavivad, J. Changes in the contents of four active diterpenoids at different growth stages in PubMed PMC

Dai, G. F., Xu, H. W., Wang, J. F., Liu, F. W. & Liu, H.-M. Studies on the novel α-glucosidase inhibitory activity and structure-activity relations for Andrographolide analogues. PubMed

Chen, D., Song, Y., Lu, Y. & Xue, X. Synthesis and in vitro cytotoxicity of andrographolide-19-oic acid analogues as anti-cancer agents. PubMed

Geng, J., Liu, J., Yuan, X., Liu, W. & Guo, W. Andrographolide triggers autophagy-mediated inflammation Inhibition and attenuates chronic unpredictable mild stress (CUMS)-induced depressive-like behavior in mice. PubMed

Paemanee, A., Hitakarun, A., Wintachai, P., Roytrakul, S. & Smith, D. R. A proteomic analysis of the anti-dengue virus activity of Andrographolide. PubMed

Luo, S. et al. Andrographolide ameliorates oxidative stress, inflammation and histological outcome in complete freund’s adjuvant-induced arthritis. PubMed

Adiguna, S. P. et al. Antiviral activities of Andrographolide and its derivatives: Mechanism of action and delivery system. PubMed PMC

Intharuksa, A., Arunotayanun, W., Yooin, W. & Sirisa-Ard, P. A. Comprehensive review of PubMed PMC

Banerjee, S. et al. Immunoprotective potential of ayurvedic herb Kalmegh ( PubMed

Raman, S., Murugaiyah, V. & Parumasivam, T. PubMed PMC

Maiti, K. et al. Enhancing bioavailability and hepatoprotective activity of Andrographolide from PubMed

Jaidee, W. et al. Kinetics of CBD, ∆ PubMed PMC

Garg, C., Sharma, P., Satija, S. & Garg, M. Stability indicating studies of

Ibrahim, M. N. & Chong, G. H. Stability of Andrographolide in

Ahammed, M. T., Sultan, M. Z., Hossain, M. S., Mahtab, M. A. & Bachar, S. C. Degradation of Andrographolide in PubMed

Lomlim, L., Jirayupong, N. & Plubrukarn, A. Heat-accelerated degradation of solid-state Andrographolide. PubMed

Plubrukarn, A., Pinsuwan, S., Ingkatawornwong, S. & Supavita, T. Stability of Andrographolide in powdered andrographis herb under accelerated conditions. PubMed

Wadeng, A. Degradation profile of chemical constituents in Andrographis herb. Preprint at: (2017). https://kb.psu.ac.th/psukb/handle/2016/11664

Jana, S. et al. Quantification and standardization of Andrographolide in PubMed

Wongkittipong, R., Prat, L., Damronglerd, S. & Gourdon, C. Solid–liquid extraction of Andrographolide from plants–experimental study, kinetic reaction and model.

Phattanawasin, P., Sotanaphun, U., Burana-Osot, J. & Piyapolrungroj, N. Isolation and characterization of the acid and base degradation products of Andrographolide. PubMed

Raksat, A. et al. Antibacterial and inhibitory activities against nitric oxide production of coumarinochromones and prenylated isoflavones from PubMed

Jaidee, W. et al. Metabolite fingerprinting of

Fitrasuah, S. I. et al. Analysis of chemical properties and antioxidant activity of Sambiloto (

Adeleye, O. A., Babalola, C. O., Femi-Oyewo, M. N. & Balogun, G. Y. Antimicrobial activity and stability of

Limsiriwong, M., Sahamethapat, A. & Kanjanapruk, P. Development and validation of UPLC method for analysis of Andrographolide from

Cava, M. P., Chan, W. R., Stein, R. P. & Willis, C. R. Andrographolide: Further transformations and stereochemical evidence; the structure of Isoandrographolide.

Pramanick, S. et al. Andropanolide and isoandrographolide, minor diterpenoids from PubMed

Chao, W. W. & Lin, B. F. Isolation and identification of bioactive compounds in PubMed PMC

Xu, Y., Wei, H., Wang, J., Wang, W. & Gao, J. Synthesis of Andrographolide analogues and their neuroprotection and neurite outgrowth-promoting activities. PubMed

Kumar, G., Singh, D., Tali, J. A., Dheer, D. & Shankar, R. Andrographolide: Chemical modification and its effect on biological activities. PubMed

Liu, L., Yan, Y., Zheng, L., Jia, H. & Han, G. Synthesis and structure anti-inflammatory activity relationships studies of Andrographolide derivatives. PubMed

Fujita, T. et al. On the diterpenes of

Rahman, M., Ayoob, I., Rehman, S., Bhat, K. A. & Ara, T. Microwave-assisted synthesis of Andrographolide analogues as potent β-glycosidase inhibitors.

Wen, Q., Jin, X., Lu, Y. & Chen, D. F. Anticomplement PubMed

Wang, G. Y. et al. Two new diterpenoid lactones isolated from PubMed

Yu, B., Zhang, Z., Liu, W., Tang, T. & Wang, P. Study on stability in vitro of Andrographolide.

Lee, S. Y., Abdullah, L. C., Rahman, R. A., Abas, F. & Ching, G. H. Stability and toxicity profile of solution enhanced dispersion by supercritical fluids (SEDS) formulated

Masuda, T. et al. Cell differentiation-inducing diterpenes from PubMed

Geoffrey, B. A. S., Prasana, J. C., Muthu, S., Abraham, C. S. & David, H. A. Spectroscopic and quantum/classical mechanics based computational studies to compare the ability of Andrographolide and its derivative to inhibit nitric oxide synthase. PubMed

Guan, H. P., Kong, L. R., Cheng, C., Lim, J. C. W. & Wong, W. S. F. Protective role of 14-deoxy-11,12-didehydroandrographolide, a noncytotoxic analogue of andrographolide, in allergic airway inflammation. PubMed

Nanduri, S. et al. Synthesis and structure-activity relationships of Andrographolide analogues as novel cytotoxic agents. PubMed

Aromdee, C., Suebsasana, S., Ekalaksananan, T., Pientong, C. & Thongchai, S. Stage of action of naturally occurring Andrographolides and their semisynthetic analogues against herpes simplex virus type 1 in vitro. PubMed

Aromdee, C. Modifications of Andrographolide to increase some biological activities: A patent review (2006–2011). PubMed