The production of inflammatory cytokines and oxidative stress are linked to metabolic derangements that ultimately lead to an elevated risk of developing chronic disease. The novel investigation that links inflammation and oxidative stress with type 2 Diabetes Mellitus dig deeply into the metabolic and cellular pathways. Recent studies focused on the therapeutic effect of berberine, and metabolic outcomes have shown positive results. However, berberine’s inhibitory effects against oxidative stress and inflammation are complex and need to be featured.
Berberine is the alkaloidal bioactive compound found in Hydratis Canadensis and Coptis Chinensis. Its beneficial activities are related to its capacity to interact with multiple proteins in the body. Besides, berberine has many metabolites associated with different beneficial functions because they interact with different cellular pathways.
The metabolism of berberine is reported to have 2 phases. In the first phase, berberine goes through demethylation, dehydrogenation, and hydroxylation. Further, berberine’s 2nd phase metabolism produces glucuronide conjugates and methylated conjugates. Nevertheless, feces and urine metabolites have been reported. Dihydroberberine (dhBBR) was found in mice feces and has been linked to the gut microbiota metabolism. On the other hand, demethylberberine-2-O-sulfate was the major berberine metabolite found in urine. Despite the ample variety of metabolites, berberine has a low plasma concentration, is poorly absorbed by the gut, and commonly remains in the gut lumen.
Common berberine metabolites
The efficacy of berberine to treat diabetes is comparable to metformin results. Besides, berberine is effective in reducing endothelial dysfunction, retinopathy, and kidney failure. Also, the use of berberine on hepatic pathologies and low toxicity are related to treatment efficacy.
The supplementation of berberine in animal model studies resulted in increased levels of GHS and a higher activity of superoxide dismutase (SOD) and glutathione peroxidase (GHS-Px). On the other hand, berberine reduced malondialdehyde (MDA) levels. The results of such studies link berberine to the scavenging of superoxide free radicals, even in a glycemic environment.
The exerted effects on the upregulation of mRNA content of SOD are mediated by SIRT1 and FOXO overexpression. Also, it suppresses nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, resulting in less ROS. This can improve diabetic conditions. Concerning the downregulation of NADH oxidase, AMPK activation is linked to a reduced arterial oxidative stress.
On the other hand, the upregulation effect of berberine over the expression of UCP2 (uncoupling protein 2) has yet to be clarified. UCP2 is located in the mitochondria membrane, and its presence is linked to reduced production of ROS and oxidative stress. Yet, more information is needed to understand the effects of UCP2 on islet B-cell. It has been reported that UCP2 could inhibit insulin secretion.
Another berberine’s antioxidant effect is related to the expression of Nrf2 (nuclear factor erythroid-2 related factor 2) pathway.
is an antioxidant transcription factor that works via the expression of NQO-1 (NADPH quinone oxidoreductase 1) and HO-1 (heme oxygenase-1).
Recent studies associate the suppression of proinflammatory cytokines with the presence of berberine. Indeed, some of these suppressed cytokines are MMP9 (matrix metalloprotease 9), TNF-α, COX2 (cyclooxygenase-2), iNOS (inducible nitric oxide synthase), MCP1 (monocyte chemoattractant protein 1), IL-6, IL-1β, CRP (C-reactive protein), and HP (hepatoglobin). Some of the berberine’s effects on downregulating cytokine production rely on its capacity to reduce serine phosphorylation while increasing tyrosine phosphorylation.
Multiple pathways mediate berberine’s antioxidant effect; the anti-inflammatory mechanisms are linked to various pathways, some of them shared with the antioxidant pathway.
Not only the AMPK pathway is involved in the antioxidant effects of berberine. In fact, studies show that in the case of an AMPK blockage, berberine could not intervene with the synthesis of COX-2 and iNOS. Therefore, the expression of prostaglandins and excessive release of nitric oxide augmented IR’s development, contributing to the DM pathogenesis.
Another inflammation-induced pathway, MAPK (mitogen-activated protein kinase), could be downregulated by AMPK and berberine activation.
P38 is a mitogen-activated protein kinase with extensive effects in inflammatory pathways. Its conjugation with berberine has brought conflicting findings. In fact, some reports show that their combined actions could lead to glucose uptake by L6 cells, but other studies found that these results could not be reproduced.
However, the Nrf2 activation and nuclear translocation have been associated with berberine and the activation of P38 and AMPK pathways. Therefore, the expression of proinflammatory cytokines has been reduced by these actions.
The NF-κB pathway can be stimulated by glucose, fatty acids, and TNF-a, as well as the activation of IκB kinase- β (IKK-β) through serine phosphorylation (ser181). However, the supplementation of berberine resulted in a decrease of IKK-β and further inhibited the nuclear transfer of NF-κB. Therefore, a reduction in the synthesis of proinflammatory cytokines like IL-6, iNOS, COX2, and TNF-α contributes to enhanced DM results.
The most common berberine dosage used in clinical studies ranges between 0.2-10g/day. In fact, the intervention with these amounts of berberine resulted in a 20-40% reduction in blood glucose level. It has been reported that these results resemble the effects of metformin and rosiglitazone. Despite the clinical uses, anti-inflammatory, and antioxidant properties, berberine needs to be further explored.
- 1 scoop veggie protein powder
- 1 tablespoon ground flaxseed
- 1/2 banana
- 1/2 cup blackberries
- 1/2 teaspoon cinnamon
- Non-dairy milk or water
Blend well, add water or milk depending on desired consistency.
-Ana Paola Rodríguez Arciniega. Master in Clinical Nutrition.
Ma, Xueling, et al. “The pathogenesis of diabetes mellitus by oxidative stress and inflammation: its inhibition by berberine.” Frontiers in Pharmacology 9 (2018): 782.
Wang, Kun, et al. “The metabolism of berberine and its contribution to the pharmacological effects.” Drug metabolism reviews 49.2 (2017): 139-157.
Cicero, Arrigo FG, and Alessandra Baggioni. “Berberine and its role in chronic disease.” Anti-inflammatory Nutraceuticals and Chronic Diseases. Springer, Cham, 2016. 27-45.
Dr. Alex Jimenez’s Blog Post
Our information scope is limited to chiropractic, musculoskeletal, physical medicines, wellness, sensitive health issues, functional medicine articles, topics, and discussions. We provide and present clinical collaboration with specialists from a wide array of disciplines. Each specialist is governed by their professional scope of practice and their jurisdiction of licensure. We use functional health & wellness protocols to treat and support care for the musculoskeletal system’s injuries or disorders. Our posts, topics, subjects, and insights cover clinical matters, issues, and topics that relate and support, directly or indirectly, our clinical scope of practice.* Our office has made a reasonable attempt to provide supportive citations and has identified the relevant research study or studies supporting our posts. We also make copies of supporting research studies available to the board and or the public upon request. We understand that we cover matters that require an additional explanation of how it may assist in a particular care plan or treatment protocol; therefore, to further discuss the subject matter above, please feel free to ask Dr. Alex Jimenez or contact us 915-850-0900. The provider(s) Licensed in Texas*& New Mexico*
Online Appointments or Consultations: https://bit.ly/Book-Online-Appointment
Online Physical Injury / Accident Intake Form: https://bit.ly/Fill-Out-Your-Online-History
Online Functional Medicine Assessment: https://bit.ly/functionmed
Spinal decompression surgery could be a treatment option discussion with a doctor to relieve nerve… Read More
Individuals with ankylosing spondylitis have a new treatment option that was previously used for rheumatoid… Read More
A healthy microbiota is considered to have rich biodiversity and functions symbiotically with its host… Read More