Centella asiatica has transitioned from traditional herbal remedy to one of the most respected active ingredients in modern dermatology and skincare. While the term “Cica” is now familiar to many consumers, the science beneath Centella’s efficacy is richly nuanced and rooted in well-characterized molecular pathways that go far beyond simple soothing. In this article, we explore the cutting-edge biology behind Centella asiatica, with a focus on how specific compounds like asiaticoside and madecassoside orchestrate skin repair and inflammation control — and how extract versus fermentation filtrates differ in biological impact.
- The Molecular Landscape of Skin Repair
Unlike generic herbal extracts, Centella asiatica’s clinical potential stems from a defined set of pentacyclic triterpenoid glycosides, especially asiaticoside and madecassoside, which have been shown to activate cellular pathways critical to skin regeneration and wound healing.
- a) Activation of Fibroblasts and Collagen Synthesis
Fibroblasts are the “workhorses” of dermal repair — they synthesize collagen and extracellular matrix (ECM) proteins that restore structural integrity after injury. Asiaticoside has been shown to stimulate fibroblast proliferation and enhance collagen type I and III synthesis, largely through modulation of TGF-β/Smad signaling pathways, which regulate ECM production and scar tissue formation.
This signaling cascade not only increases collagen deposition but also supports epidermal remodeling and tensile strength, making it scientifically valuable in wound care and anti-aging applications.
b) Angiogenesis and ECM Remodeling
Both asiaticoside and madecassoside can enhance expression of VEGF and FGF, key growth factors that promote angiogenesis — the formation of new blood vessels supplying nutrients and oxygen to healing tissues.
This effect accelerates the wound closure process, supporting rapid recovery from mechanical damage, burns, or post-procedure resurfacing.
- Controlling Inflammation: NF-κB, Cytokines, and Antioxidant Balance
Inflammation is a double-edged sword in skin healing: necessary for initial defense but harmful if chronic or excessive. Centella’s triterpenes modulate this balance via several pathways:
- a) Inhibition of Pro-inflammatory Signaling
A core mechanism is suppression of NF-κB, a central transcription factor that drives production of pro-inflammatory cytokines like TNF-α, IL-6, and IL-1β. Bioactive compounds, especially madecassoside, significantly reduce NF-κB activation, leading to lower inflammatory mediator levels and faster resolution of the inflammatory phase.
- b) Antioxidant Defence via Nrf2 Activation
Centella asiatica also activates the Nrf2 pathway — a master regulator of antioxidant response — increasing enzymes like SOD, catalase, and HO-1 that neutralize reactive oxygen species (ROS). This antioxidant boost is crucial for limiting oxidative damage during inflammation and contributes to barrier integrity and anti-aging benefits.
- Asiaticoside vs. Madecassoside: Distinct Roles Within the Herb
Although both compounds derive from the same plant, they exhibit complementary but distinct biological roles:
- Asiaticoside: Strongly linked to collagen synthesis, fibroblast activation, and structural repair via TGF-β and Smad pathways.
- Madecassoside: Demonstrates potent anti-inflammatory and antioxidant activity, with robust NF-κB inhibition and cytokine suppression, often resulting in faster symptom relief in inflammation models.
Some in vivo studies suggest madecassoside may even outperform asiaticoside in wound closure speed and pattern, underscoring its potential as a targeted actives in formulations emphasizing rapid skin recovery.
This differentiation underscores the value of ingredient standardization in manufacturing: quantifying ratios of key actives allows predictable performance rather than relying on variable whole-plant extracts.
- Extract vs. Ferment Filtrate: What’s the Difference?
While traditional Centella extracts deliver triterpenoid glycosides and flavonoids directly from plant material, fermented filtrates introduce an additional layer of biochemical complexity:
- a) Fermentation-Enhanced Bioactivity
Preliminary research shows that Lactobacillus-fermented Centella asiatica extract can lead to enhanced suppression of pro-inflammatory mediators in cell models compared with non-fermented extracts. Fermentation may modify the phytochemical profile, potentially improving bioavailability or transforming compounds into more active, easier-to-absorb metabolites.
References:
Bylka, W., Znajdek-Awiżeń, P., Studzińska-Sroka, E., & Brzezińska, M. (2014). Centella asiatica in cosmetology. Postępy Dermatologii i Alergologii, 31(1), 46–49.
Coldren, C. D., Hashim, P., Ali, J. M., Oh, S. K., Sinskey, A. J., & Rha, C. (2003). Gene expression changes in the human fibroblast induced by Centella asiatica triterpenoids. Planta Medica, 69(8), 725–732.
Gohil, K. J., Patel, J. A., & Gajjar, A. K. (2010). Pharmacological review on Centella asiatica: A potential herbal cure-all. Indian Journal of Pharmaceutical Sciences, 72(5), 546–556.
Hashim, P. (2011). The effect of Centella asiatica, Triticum aestivum and Curcuma longa on collagen synthesis in human skin fibroblasts. African Journal of Biotechnology, 10(69), 15790–15795.
James, J. T., & Dubery, I. A. (2009). Pentacyclic triterpenoids from the medicinal herb Centella asiatica (L.) Urban. Molecules, 14(10), 3922–3941.
Li, H., Gong, X., Zhang, L., Zhang, Z., & Luo, F. (2019). Madecassoside attenuates inflammatory response in LPS-induced macrophages via inhibition of NF-κB signaling pathway. International Immunopharmacology, 72, 261–268.
Maquart, F. X., Bellon, G., Gillery, P., Wegrowski, Y., Borel, J. P., & Caron, G. (1999). Stimulation of collagen synthesis in fibroblast cultures by a triterpene extracted from Centella asiatica. Connective Tissue Research, 40(1), 33–39.
Orhan, I. E. (2012). Centella asiatica (L.) Urban: From traditional medicine to modern medicine with neuroprotective potential. Evidence-Based Complementary and Alternative Medicine, 2012, 946259.
Park, B. C., Kim, M. S., Choi, H. O., Kim, D. W., & Hong, S. P. (2017). The effect of Centella asiatica on wound healing and scar formation: A systematic review. Journal of Cosmetic Dermatology, 16(3), 310–317.
Seo, J. Y., Choi, H. R., Rhie, G. E., Youn, C. S., & Kim, K. H. (2006). Effects of Centella asiatica extract on the expression of matrix metalloproteinases in human dermal fibroblasts. International Journal of Dermatology, 45(12), 1463–1469.
Shukla, A., Rasik, A. M., & Dhawan, B. N. (1999). Asiaticoside-induced elevation of antioxidant levels in healing wounds. Phytotherapy Research, 13(1), 50–54.
Wu, F., Bian, D., Xia, Y., Gong, Z., Tan, Q., Chen, J., Dai, Y., & Tong, Q. (2012). Identification of major active ingredients responsible for burn wound healing of Centella asiatica herbs. Evidence-Based Complementary and Alternative Medicine, 2012, 848093.
Zhao, J., Zhang, Q., Zhou, Y., Cao, H., & Yang, Y. (2022). Enhanced anti-inflammatory activity of fermented Centella asiatica extract through modulation of NF-κB and oxidative stress pathways. Plants, 11(22), 3416.
