INDENA

Indena Berbevis®: Keep your metabolism balanced, naturally

 

Berberine, a long history of a natural treasure

 

Berberine is a plant alkaloid with a long history of medicinal use in both Ayurvedic and Chinese medicine. It is present in Hydrastis Canadensis (goldenseal), Coptis chinensis (Coptis or goldenthread), Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), and Berberis aristata (tree turmeric). The berberine alkaloid can be found in the roots, rhizomes, and stem bark of the plants.

Berberidaceae, the barberry family of the buttercup order (Ranunculales), comprises 14 genera and 701 species of perennial herbs and shrubs.[1] In the Berberidaceae family, the genus Berberis comprises of around 450–500 species, which represent the main natural source of berberine.

Among the various species of Berberis genus, Berberis aristata DC is one of the most important species due to its wide medicinal properties and its occurrence has reported from sub-tropical areas (1800-3000 m above sea level) of the mountain state of Uttarakhand and Himachal Pradesh. It is used in various crude drug formulations and in different traditional and homeopathic medicines since ancient times.

It is erect spinous shrub, which is hard, yellowish useable part commonly employed in Indian medicine system. The fruits of the species are eaten by inhabitants for curing various diseases.

Berberis spp. has various pharmacological actions. It has been used in traditional medicine for its antimicrobial, antiprotozoal, antidiarrheal and antitrachoma activity.[2] Berberine is a quaternary ammonium salt derived from isoquinoline alkaloid and it is supported by reliable scientific literature proving its health benefits in multifactorial conditions, including the support in controlling healthy blood levels.[3] The berberine alkaloid can be found in the roots, rhizomes, and stem bark of the plants.

Specifically, berberine’s proven effectiveness in the treatment of multifactorial conditions is related to its so-called “Cloud Effect”: its pleiotropic effect simultaneously targets both root causes (e.g. low-grade chronic inflammation, oxidative stress, gut microbiota modulation) and marks (e.g. insulin levels) through the modulation of several cellular targets (e.g. AMPK, mitochondria, insulin-receptor, key metabolic and pro-inflammatory enzymes, etc.). This helps optimize peripheral blood metabolic profiles by modulating plasma sugar, insulin and lipids levels, thus resulting as a precious resource for the metabolic wellbeing.[4]

Indena’s BERBEVIS®: berberine never so effective

Berberine has a poor bioavailability, like many natural compounds. In the specific case, it is due to several factors: poor absorption from the gut (<5%), rapid metabolism in the body, conversion to ionic form under physiological conditions, self-aggregation at low pH values, low solubility in the gastrointestinal tract, low ability to permeate the gut wall, efflux of P-glycoprotein (Pgp) located in the epithelial cell membrane. For these reasons high dosages are traditionally recommended for berberine, that means low tolerability and gastrointestinal side effects.

To manage such an issue, which concerns many natural ingredients, Indena developed since years Phytosome®, the proprietary biomimetic strategy for the delivery of natural ingredients, allowing human body to absorb them in the best possible way. It is a fundamental asset, and an internationally recognized scientific reference for the delivery systems of natural active ingredients. Phytosome® combines food-grade sunflower lecithin with botanical and natural substances maintaining the original components’ profile and benefits. Lecithins are natural surfactants which take part, together with bile salts, to the physiological absorption process of compounds and form the lipid bilayer structure of cell membranes. As amphipathic molecule consisting of a positively charged head group and two neutral tail acyl moieties, lecithin acts as inhibitor of self-aggregation, leaving natural compounds into a dispersed state more readily absorbed. Numerous scientific studies have proven that Phytosome® system delivery offers optimized human pharmacokinetic profiles and effectiveness compared to non-formulated equivalent compounds.

Knowing, respecting and enforcing the uniqueness of nature, Indena designs and formulates every single Phytosome® according to the properties of the specific natural ingredient, in order to optimize its health benefits. Working on berberine, Indena developed BERBEVIS®, a new and innovative  Phytosome® composition, based on some scientifically proven evidences:

  • berberine in a rhizome extract naturally rich in proteins showed better intestinal absorption and plasma exposure than pure berberine5: that’s why Indena decided to include a natural vegetable protein carrier within the Phytosome® matrix, using pea proteins;
  • the inclusion of a powerful, natural antioxidant such as grape seed extract within the Phytosome® matrix may protect the intestinal mucosa against the known gastrointestinal adverse effects of traditional berberine, optimizing its tolerability profile.[5]

Remarkably, a human pharmacokinetic study has confirmed that BERBEVIS® can optimize berberine bioabsorption, improving the substance’s bioavailability on molar basis and with observed dose linearity.

In vitro studies have been also made to further investigate both bioaccessibility and tolerability of Indena’s BERBEVIS®. Bioaccessibility is referred to bioactive compounds and nutrients, and represents the amount of an ingested nutrient that is released from a matrix becoming available to be absorbed after undergoing the digestion process. On the other hand, it was important to verify berberine Phytosome® tolerability compared to traditional Berberis extracts, which, due to their poor oral absorption, need to be used at high dosages that result in gastrointestinal adverse effects.

The in vitro studies results showed that:

  • Phytosome® formulation enhances berberine solubility in gastrointestinal fluids;
  • Phytosome® formulation has a better bioaccessibility than unformulated Berberis extract, improving the amount of berberine released into the gastrointestinal tract and available for absorption;
  • Phytosome® formulation has a higher safety profile than unformulated Berberis extract with the absence of negative impact on intestinal membranes;
  • BERBEVIS® appears to be suitable for a long-term administration.

BERBEVIS®:   Your natural ally for a healthy metabolism

The medicinal plants might provide a useful source of new oral hypoglycemic compounds for development of pharmaceutical entities or as a dietary adjunct to existing therapies. Few of the plants used for the treatment of diabetes have received scientific or medicinal scrutiny and even the WHO expert committee on diabetes recommends that this area warrant further attention.[2]

Exactly to check the effectiveness of berberine Phytosome® on keeping healthy blood glucose level, BERBEVIS® has been used to supplement the diet of subjects enrolled in a human study focused on PCOS (Polycystic Ovary Syndrome) with the aim for the first time to measure the whole range of marks modulation. PCOS is a complex, multifactorial, endocrine-metabolic disorder. Berberine  has a multiple mechanism of action on multifactorial conditions. In PCOS subject’s metabolic health is impaired mainly due to  insulin resistance (IR), i.e. the body’s inability to respond to the amount of insulin produced by the pancreas, leading to unhealthy and excessive blood sugar levels that can potentially be harmful.

According to the study’s multiple endpoints data, BERBEVIS® diet support emerged as the winning multi-target approach to metabolic health
maintenance thanks to an effective positive effect on blood sugar levels, because:

  • it optimizes insulin levels effectively, after as few as 30 days of treatment, achieving a remarkable result at the end of the study (based on HOMA index value);
  • it noticeably modulates the blood sugar profile, optimizing both blood glycaemia and insulin;
  • a favourable safety profile was reported, with no major adverse events.

Furthermore, the following secondary endpoints were reported:

  • BERBEVIS® effectively supports metabolic health, having a positive effect on blood lipid profile, body composition and fostering the redistribution of adipose tissue even in subjects who are not following a low-calorie diet;
  • it promotes hormonal balance;
  • it has a positive effect on low-grade chronic inflammation, balancing major inflammation biomarkers;
  • it’s also helpful for healthy skin, being acne a typical condition of PCOS highly affecting quality of life.

All in all, BERBEVIS® is a potent, natural health-food ingredient that might help blood sugar control in a plethora of multifactorial challenges, which represent one of our time’s main global health targets.

 

References

  1. https://www.britannica.com/plant/Berberidaceae
  2. Chander, Vikas, et al., The Journal of Phytopharmacology 6.1 (2017): 53-58.
  3. Feng, Xiaojun, et al., Theranostics 9.7 (2019): 1923.
  4. Kong, Wei-Jia, et al., Pharmacology & therapeutics 209 (2020): 107496.
  5. Ma, Bing-Liang, et al., Scientific reports 6.1 (2016): 1-11.

 

For more info:

Email: laura.bo@indena.com
External Communication and Sustainability

www.indena.com

 

 

 

Indena is the leading company dedicated to the identification, development and production of high quality active principles derived from plants, for use in the pharmaceutical and health food industries. Backed up by a century of botanical experience, the company owns 100 patent families, has published more than 1000 scientific studies and co-operates with the world’s most prestigious universities and private research institutions. Indena employs over 900 staff, investing a significant amount of its annual turnover in research, making this activity the key to its success. Headquartered in Milan, Indena has 4 production sites and 5 international branches throughout the world and manages sales in more than 80 countries. The company’s experts communicate and interact constantly with the major international regulatory authorities and cooperate on the update of all the main pharmacopoeias.

Today Indena has further expanded its CDMO offer encompassing new services. In particular, a kilolab to handle semi- synthetic and total synthetic APIs that require high containment (OEL of 20 ng/m3), a new multipurpose GMP pilot plant, a multipurpose fermentation suite and large-and-mid size spray dryers working with organic solvents.