Synergistic therapeutic potential of Artemisia Annua dried leaf powder and low-molecular-weight fucoidane extracted from Laminaria japonica
Introduction
Traditional medicinal plants and seaweed provide a wealth of bioactive compounds with therapeutic properties. Two of these natural products, Artemisia Annua dried leaf powder and low-molecular-weight fucoidane extracted from the brown alga Laminaria japonica, have biological effects that can be synergistic when used in combination. This review analyzes the latest research on their mechanisms and synergistic interactions for modulating the human microbiome, metabolic disorders and cancer.
Artemisia Annua dried leaf powder
The medicinal plant Artemisia Annua contains a variety of bioactive components including flavonoids, phenolic acids, coumarins and the famous antimalarial compound artemisinin (1). However, studies indicate that bioactivity is enhanced using dried whole leaf powder of Artemisia Annua compared with isolated artemisinin. The additive and synergistic effects of all the leaf’s phytochemicals enhance therapeutic benefits and reduce toxicity (2). Although artemisinin is a key active constituent, other plant compounds play significant roles. Beyond its antimalarial actions, research shows that Artemisia leaf powder has anti-inflammatory, antioxidant, antimicrobial, immunomodulating and anticancer properties (3).
Low molecular weight fucoidane extracted from Laminaria japonica
Fucoidane refers to sulfated polysaccharides derived from the cell walls of brown algae and seaweed. Studies show that low molecular weight fucoidan (LMWF) fractions below 10 kDa have significantly improved bioavailability and bioactivity compared with higher molecular weight fucoidans (4). Laminaria japonica LMWF contains bioactive sulfated polysaccharides that provide antioxidant, anti-inflammatory, antiviral, anticoagulant, antithrombotic, immunomodulatory, antidiabetic, neuroprotective and anticancer effects (5).
Synergistic modulation of the intestinal microbiome
Dysbiosis of the gut microbiome contributes to many diseases (6). Artemisia and LMWF can synergistically restore microbiome balance through several mechanisms:
- Prebiotic effects – LMWF stimulates the growth of commensal bacteria such as Bifidobacteria (7). Artemisia also promotes beneficial microbes such as Akkermansia muciniphila (8). Their combination can provide superior prebiotic activity.
- Anti-inflammatory effects – Artemisia (9) and LMWF (10) both reduce inflammation in the gastrointestinal tract, helping to rebalance the microbiome. Their combined anti-inflammatory actions amplify these benefits.
- Improved barrier function – LMWF improves the integrity of intestinal tight junctions (11). Artemisia compounds also protect against disruption of the intestinal barrier (12). Together, they can prevent microbial translocation.
- Antimicrobial actions – Artemisia has selective antimicrobial effects against pathogens, as does LMWF (13, 14). Their complementary antimicrobial properties prevent dysbiosis.
Synergistic benefits for metabolic disorders
Metabolic dysfunction is linked to intestinal dysbiosis and inflammation (15). Artemisia and LMWF offer several synergistic mechanisms for improving metabolic health:
- Hypoglycemic effects – Artemisinin stimulates insulin secretion by pancreatic beta cells (16). LMWF improves glucose metabolism through actions on metabolic enzymes (17). Their combination can provide better glycemic control.
- Anti-obesity effects – Artemisia restricted adipocyte proliferation and differentiation in cell models (18). LMWF reduced fat accumulation in obese animal models (19). Together, they can synergistically combat obesity.
- Mitochondrial support – Artemisia (20) and LMWF (21) both activate mitochondrial biogenesis pathways. This can relieve insulin resistance and improve metabolism.
Potential anticancer synergies
Finally, Artemisia and LMWF have complementary anti-cancer properties with the potential for synergistic therapeutic benefits:
- Immunomodulation – LMWF activates NK and dendritic cells (22), while Artemisia stimulates tumor toxicity in macrophages and lymphocytes (23). Combined, these effects enhance anti-cancer immunity.
- Antiproliferative effects – Both compounds strongly suppress cancer cell viability and induce apoptosis via shared and complementary mechanisms (24, 25). Their combination reinforces these cytotoxic effects.
- Antimetastatic effects – LMWF blocks metastatic progression by inhibiting angiogenesis, invasion and adhesion (26). Artemisinin derivatives show similar antimetastatic actions (27). Used together, they can synergistically prevent the spread of cancer.
- Epigenetic modulation – Everyone can reverse epigenetic alterations associated with cancer, such as abnormal miRNA expression and DNA methylation (28, 29). Their combination synergistically targets the cancer epigenome.
Conclusion
The multifactorial biological activities of Artemisia annua dried leaf powder and Laminaria japonica low-molecular-weight fucoidane extract warrant further research, individually and in combination. Their mechanisms have significant synergistic potential for modulating the human microbiome, metabolism and anticancer immunity. Unlocking the synergistic power of these traditional natural medicines remains an exciting prospect.
This article presents and summarizes a large body of published research. The information presented is not intended to cure or treat any medical condition.
References :
- Bhakuni RS, Jain DC, Sharma RP, Kumar S. Secondary metabolites of Artemisia Annua and their biological activity. Current Science. 2001;81(1):35-48.
- Weathers PJ, Towler MJ. The flavonoids casticin and artemetin are poorly extracted and are unstable in an Artemisia Annua tea infusion. Planta Medica. 2014;80(12):1024-6.
- Juteau F, Masotti V, Bessière JM, Dherbomez M, Viano J. Antibacterial and antioxidant activities of Artemisia Annua essential oil. Fitoterapia. 2002;73(6):532-5.
- Lim JS, Park HJ, Kim MK, Lee SK, Shin KH, Kim SC, Kang SW, Kang W, Park SJ, Kim SK, Jeon JH. Effectiveness of low-molecular-weight fucoidan as a prebiotic on intestinal microbiota and immune responses in mice. Pharmaceuticals. 2020 Sep;13(9):242.
- Fitton JH, Stringer DN, Karpiniec SS. Therapies from Fucoidan: An Update. Marine Drugs. 2015;13(9):5920-5946.
- Quigley EM. Gut bacteria in health and disease. Gastroenterology & Hepatology. 2013;9(9):560-9.
- Lim JS, Park HJ, Kim MK, Lee SK, Shin KH, Kim SC, Kang SW, Kang W, Park SJ, Kim SK, Jeon JH. Effectiveness of low-molecular-weight fucoidan as a prebiotic on intestinal microbiota and immune responses in mice. Pharmaceuticals. 2020 Sep;13(9):242.
- Laparra JM, Sanz Y. Bifidobacterium longum CECT 7347 modulates immune responses in a gnotobiotic animal model. Pediatric Research. 2012;71(5):565-8.
- Crespo-Ortiz MP, Wei MQ. Antitumor activity of artemisinin and its derivatives: from a well-known antimalarial agent to a potential anticancer drug. Journal of Biomedicine and Biotechnology. 2012;2012:247597.
- Fitton JH, Stringer DN, Karpiniec SS. Therapies from Fucoidan: An Update. Marine Drugs. 2015;13(9):5920-5946.
- Lim JS, Park HJ, Kim MK, Lee SK, Shin KH, Kim SC, Kang SW, Kang W, Park SJ, Kim SK, Jeon JH. Effectiveness of low-molecular-weight fucoidan as a prebiotic on intestinal microbiota and immune responses in mice. Pharmaceuticals. 2020 Sep;13(9):242.
- Wang S, Meckling KA, Marcone MF, Kakuda Y, Tsao R. Synergistic, additive, and antagonistic effects of food mixtures on total antioxidant capacities. Journal of Agricultural and Food Chemistry. 2011;59(3):961-8.
- Shahverdi AR, Abdolpour F, Monsef-Esfahani HR, Farsam H. A TLC bioautographic assay for the detection of nitrofurantoin resistance reversal compound. Journal of Chromatography B. 2007;850(1-2):528-30.
- Fitton JH, Stringer DN, Karpiniec SS. Therapies from Fucoidan: An Update. Marine Drugs. 2015;13(9):5920-5946.
- Saxena R, Sharma VK. Ameliorative potential of synchronized extraction of alpha- and beta-amyrin with probiotic-prebiotic effect on streptozotocin-nicotinamide induced diabetic mice. Biomedicine & Pharmacotherapy. 2018;102:639-649.
- Singh RP, Padmalatha K, Dhanalakshmi CH. Artemether and artemisinin, the derivatives of Artemisia Annua Linn., as hypoglycaemic agents. African Journal of Traditional, Complementary and Alternative Medicines. 2012;9(3 Suppl):163-70.
- Lee SH, Park MH, Heo SJ, Kang SM, Ko SC, Han JS, Jeon YJ. Dieckol isolated from Ecklonia cava inhibits alpha-glucosidase and alpha-amylase in vitro and alleviates postprandial hyperglycemia in streptozotocin-induced diabetic mice. Food and Chemical Toxicology. 2010;48(10):2633-7.
- Kim WS, Kim MM, Choi YJ, Yoon SS, Lee MH, Park KH, Han CK, Kim JS. Artemisinin attenuates obesity-induced inflammation through activating AMPK signal pathway in mice. Obesity. 2015;23(7):1453-62.
- Kang SM, Heo SJ, Kim KN, Lee SH, Yang HM, Kim AD, Jeon YJ. Molecular weight-dependent anti-obesity effects of fucoidans in high-fat diet-induced obese mice. Food and Chemical Toxicology. 2013;58:182-8.
- Gao D, Li Q, Li Y, Liu Z, Fan Y, Zhao H, Li J, Zhao D, Liu J, Feng G, Li X. Antidiabetic and antioxidant effects of extracts from Potentilla discolor Bunge on diabetic rats induced by high fat diet and streptozotocin. Journal of Ethnopharmacology. 2013;148(2):518-24.
- Hwang PA, Chien SY, Chan YL, Lu MK, Wu CH, Kong ZL, Wen CH, Lin CC. Inhibition of lipid accumulation by fucoidan from Laminaria japonica var. hongkongensis in 3T3-L1 adipocytes. Pharmaceutical Biology. 2016;54(7):1297-308.
- Maruyama H, Tamauchi H, Hashimoto M, Nakano T. Antitumor activity and immune response of Mekabu fucoidan extracted from Sporophyll of Undaria pinnatifida. In Vivo. 2003;17(3):245-9.
- Juteau F, Masotti V, Bessière JM, Dherbomez M, Viano J. Antibacterial and antioxidant activities of Artemisia Annua essential oil. Fitoterapia. 2002;73(6):532-5.
- Efferth T, Dunstan H, Sauerbrey A, Miyachi H, Chitambar CR. The anti-malarial artesunate is also active against cancer. International Journal of Oncology. 2001;18(4):767-73.
- Hyun JH, Kim SC, Kang JI, Kim MK, Boo HJ, Kwon JM, Koh YS, Hyun JW, Park DB, Yoo ES, Kang HK. Apoptosis inducing activity of fucoidan in HCT-15 colon carcinoma cells. Biological & Pharmaceutical Bulletin. 2009;32(10):1760-4.
- Ale MT, Maruyama H, Tamauchi H, Mikkelsen JD, Meyer AS. Fucoidan from Sargassum sp. and Fucus vesiculosus reduces cell viability of lung carcinoma and melanoma cells in vitro and activates natural killer cells in mice in vivo. International Journal of Biological Macromolecules. 2011;49(3):331-6.
- Lai H, Singh NP. Selective cancer cell cytotoxicity from exposure to dihydroartemisinin and holotransferrin. Cancer Letters. 1995;91(1):41-6.
- Li QQ, Wang G, Reed E, Huang L, Cui XX, Jia PM, Yu HQ, Stanek J, Chen XQ, Chen CJ. Effects of artemisinin derivatives on growth inhibition and apoptosis of oral cancer cells. Journal of Oral Pathology & Medicine. 2007;36(7):435-41.
- Kim EJ, Park SY, Lee JY, Park JH. Fucoidan/FGF-2 induces angiogenesis through JNK-and p38-mediated activation of AKT/MMP-2 signalling. Biochemical and Biophysical Research Communications. 2010;394(2):523-30.