Reginin A

Other Names

C-glycosidic ellagitannin dimerellagitannin (dimeric, C-glycosidic type)

Synopsis

Reginin A: An Encyclopedic Reference

1. Identity

1.1 Chemical and Botanical Classification

Reginin A is a naturally occurring ellagitannin — specifically, a hydrolysable tannin of the C-glycosidic subclass — isolated from plants of the genus Lagerstroemia in the family Lythraceae. Screening of Lagerstroemia speciosa plant extracts identified lagerstroemin, flosin B (the C1-epimer of lagerstroemin), and reginin A as activators of glucose transport using rat fat cells; all three are characteristic C-glycosidic ellagitannins of the plant. Reginin A is structurally closely related to lagerstroemin and flosin B and belongs to the same polyphenolic tannin family.

Ellagitannins are a hydrolysable tannin subgroup biosynthesized via the shikimic acid–gallic acid–pentagalloylglucose pathway. The structural elucidation of reginin A and its companion compound reginin B was reported in a landmark phytochemical study documented in the Chemical and Pharmaceutical Bulletin series on tannins and related compounds. The method involved preparation of aminoalditol derivatives of hydrolyzable tannins and its application to the structure elucidation of reginins A and B and flosin A, isolated from Lagerstroemia flos-reginae Retz, published in Chem. Pharm. Bull. 1991;39:639–646.

1.2 Primary Botanical Source

The primary botanical source of reginin A is Lagerstroemia speciosa (L.) Pers., commonly known as banaba (the Tagalog name used in the Philippines), "Pride of India," and "Queen's crepe myrtle." It is a tree species reaching up to 15 metres in height, with large, leathery, oblong leaves and flowers in various colours including white, purple, and lavender; it is widely distributed across Asia and Australia, native to regions including China, Cambodia, Thailand, Vietnam, Indonesia, Malaysia, and the Philippines. Reginin A has also been isolated from the related species Lagerstroemia flos-reginae Retz (also known as Lagerstroemia flos-reginae or "queen's flower"), from which further structural work on tannins resulted in the isolation of the monomeric ellagitannin flosin B and the dimeric ellagitannins reginins C and D.

Both Lagerstroemia flos-reginae and L. speciosa (banaba) belonging to the family Lythraceae are particularly rich in C-glycosidic tannins. Chemical compounds isolated from L. speciosa extract include corosolic acid, lagerstroemin, flosin B, and reginin A.

1.3 Common Forms and Preparations

In the context of dietary supplementation and research, reginin A is not typically commercialized or administered as an isolated, pure compound. Instead, it occurs as one constituent of broader banaba leaf extracts, which are the commercially available form. Banaba has become a popular ingredient in health supplements, with banaba leaf extracts refined into capsules, teas, and powders, often used to help address blood glucose and metabolic concerns. Lagerstroemia speciosa (banaba) has become relatively popular in the form of health-promoting tea products in Eastern Asia and the United States.

Most studies have focused on corosolic acid, which is isolated with an organic solvent from the leaves of the plant and is used to standardize banaba extracts. Because reginin A is water-soluble, it is predominantly found in aqueous (water-based) and aqueous-acetone extracts of banaba leaves, rather than in corosolic-acid-standardized, lipid-soluble fractions. Some studies indicate that ellagitannins in water-soluble fractions may be responsible for at least some of the insulin-like activity of banaba.

2. Traditional and Historical Use

2.1 Philippines

The most well-documented traditional use of the banaba plant — and thus its constituent reginin A — originates in the Philippine archipelago, where the leaves have been employed medicinally for centuries. The leaves of Lagerstroemia speciosa (Lythraceae), a Southeast Asian tree more commonly known as banaba, have been traditionally consumed in various forms by Filipinos for treatment of diabetes and kidney-related diseases. The leaves of Lagerstroemia speciosa, known locally as banaba, have been traditionally prepared as a tea for promoting general wellness, with records indicating its use dating back to the 16th century in local herbals for managing common ailments.

Only in the Philippines are the dried and shredded banaba leaves known to be used as a treatment for diabetes and kidney disease. Banaba herb is one of the 69 herbal plants promoted by the Philippine Department of Health (DOH). This governmental endorsement reflects the depth of its traditional integration into Filipino folk medicine.

2.2 Vietnam, Taiwan, Japan, and Southeast Asia

The leaves and other parts of banaba are used widely in the Philippines, Taiwan, and Japan as a tea preparation, and in Vietnam, the plant's young leaves are consumed as vegetables, while its old leaves and mature fruit are used in traditional medicine for reducing glucose in blood. The popular use of banaba in the Philippines was noticed and led to its introduction in Japan.

2.3 South Asia

Traditional folk medicine practitioners have used L. speciosa to treat hypertension, urinary disorders, hyperlipidemia, diarrhea, diabetes, and pain. Its leaves exhibit diuretic, decongestant, anti-diabetic, and anti-obesity properties, while the roots are utilized for treating mouth ulcers, the bark serves as a stimulant and fever-reducing agent, and the seeds possess narcotic properties.

2.4 Preparations and Their Contexts

In traditional practice, banaba leaves (the primary source of reginin A) were typically prepared as a decoction or hot-water tea. Garcia published the first formal research on banaba's insulin-like hypoglycemic effect as early as 1940, building on this indigenous knowledge. It was not until 50 years after Garcia's first publication that scientific interest in banaba's potential for the treatment of diabetes resurfaced. This gap underscores how traditional use preceded and ultimately catalyzed modern phytochemical investigation.

It bears emphasis that traditional records do not distinguish reginin A as a specific compound — the preparation was always a whole-leaf extract or tea. Direct references to reginin A as an isolated entity are therefore a product of modern analytical chemistry, not traditional ethnobotany.

3. Key Constituents and the Phytochemical Context of Reginin A

3.1 Position Among Banaba's Active Compounds

More than 40 compounds have been identified and documented from banaba leaves, primarily containing triterpenes such as ursolic acid and corosolic acid. In addition, the leaves contain significant concentrations of hydrolysable tannins. Leaves of L. speciosa contain abundant tannins (up to 40%), with six ellagitannins — including lagerstroemin, flosin B, stachyurin, casuarinin, casuariin, and 2,3-(S)-hexahydroxydiphenoyl-α/β-D-glucose — and four methyl ellagic acid derivatives identified from leaves, which exhibit strong activity in promoting insulin-like glucose absorption.

Reginin A thus belongs to a larger ensemble of bioactive tannins in banaba. Multiple studies have suggested that the hypoglycemic activity of Lagerstroemia plants results from the combined effects of various chemical components, including corosolic acid, ursolic acid, PGG (1,2,3,4,6-penta-O-galloyl-β-D-glucose), lagerstroemin, flosin B, reginin A, asiatic acid, valoneaic acid dilactone, and others.

3.2 Classification as a C-Glycosidic Ellagitannin

Reginin A is classified as a C-glycosidic ellagitannin. Ellagitannins are one of the bioactive groups produced by some medicinal plants, biosynthesized via the shikimic acid–gallic acid–pentagalloylglucose pathway. The C-glycosidic designation refers to the linkage by which the tannin's galloyl-derived ester units are attached to a glucose core via a carbon–carbon bond, conferring greater resistance to hydrolysis compared with non-C-glycosidic variants.

On the basis of chemical and spectroscopic evidence, the structure of the closely related compound flosin B was determined to be a C-glycosidic ellagitannin possessing a valoneic acid dilactonyl group, while reginins C and D were characterized as dimeric ellagitannins in which a pedunculagin moiety is connected to pterocarinin A and casuarinin moieties, respectively, through a carbon-to-oxygen bond. Reginin A itself was identified by NMR analysis and optical rotation measurement.

3.3 Isolation Method

Glucose transport enhancers were searched for in Lagerstroemia speciosa, a Philippine local herbal medicine used for diabetes mellitus. Bioassay-guided fractionation of the aqueous acetone extract of the leaves afforded three active ellagitannins — lagerstroemin, flosin B, and reginin A — identified by NMR and optical rotation; these compounds increased glucose uptake of rat adipocytes and could be responsible for lowering the blood glucose level. Ellagitannins can be isolated by cascade extraction procedures followed by column chromatography and preparative HPLC methods.

4. Mechanisms of Action

4.1 GLUT4-Mediated Glucose Uptake

The most rigorously investigated mechanism attributable to reginin A (and its co-occurring ellagitannins in banaba) is stimulation of cellular glucose uptake via the glucose transporter type 4 (GLUT4). Ellagitannin compounds — specifically lagerstroemin, flosin B, and reginin A — have been shown to regulate blood glucose levels; these compounds promote glucose uptake by activating glucose transporter type 4 (GLUT4), a protein responsible for transporting glucose from the blood into muscle cells and adipocytes.

Tested ellagic acid derivatives demonstrated inhibitory effects on glucose transport for the first time, suggesting that tannins may stimulate glucose uptake like insulin by activating GLUT4; moreover, three tannins isolated from L. speciosa — lagerstroemin, flosin B, and reginin A — increased glucose absorption in rat adipocytes.

4.2 Insulin Receptor Activation

Research into the closely related compound lagerstroemin has clarified a plausible molecular pathway also relevant to the ellagitannin class as a whole. Lagerstroemin is believed to exert insulin-like effects through a mechanism different from insulin itself by possibly binding to the extracellular portion of insulin receptors in a way that induces insulin receptor activation. The insulin-like activity of lagerstroemin was indicated by increases in glucose uptake by rat adipocytes and by increased tyrosine-phosphorylation in Chinese hamster ovary cells expressing human insulin receptors.

A hexoxydiphenic acid derivative (the class to which lagerstroemin and, by structural analogy, reginin A belong) has an insulin-like action via glucose uptake-promoting activity in peripheral tissues through GLUT4 present in cells, and was found to have an effect via phosphatidylinositol 3-kinase (PI3K); lagerstroemin and its epimers flosin B and reginin A also have this insulin-like action.

4.3 Inhibition of Adipocyte Differentiation

In addition to glucose transport activation, casuarinin and lagerstroemin were identified as active components in the stimulation of insulin-like glucose uptake and in the inhibition of adipocyte differentiation in 3T3-L1 cells. This anti-adipogenic activity is of interest in the context of anti-obesity research.

4.4 Multiple Metabolic Mechanisms for Banaba as a Whole

The beneficial effects of banaba and corosolic acid with respect to various aspects of glucose and lipid metabolism appear to involve multiple mechanisms, including enhanced cellular uptake of glucose, impaired hydrolysis of sucrose and starches, decreased gluconeogenesis, and the regulation of lipid metabolism; these effects may be mediated by PPAR and other signal transduction factors. While these mechanisms have been studied most thoroughly for corosolic acid and lagerstroemin individually, reginin A contributes to the overall ellagitannin-mediated component of banaba's activity.

4.5 Antioxidant Activity

The biological activities of ellagitannins are caused by molecular bonding between the ellagitannin and other compounds — especially proteins — that form complex compounds and change physiological processes in cells or tissues. Biological activities of ellagitannins include anti-diabetic, anti-microbial, anti-viral, anti-hypertensive, antioxidative, and anti-cancer or anti-tumor activities. The antioxidant properties of L. speciosa tea, particularly when subjected to freeze-drying during the drying process, were significantly enhanced, possibly attributed to ellagitannins such as lagerstroemin, flosin, and reginin.

5. Scientific Evidence by Area of Use

5.1 Blood Glucose Regulation and Anti-Diabetic Activity

In Vitro Evidence

Glucose transport enhancers were searched for in Lagerstroemia speciosa, a Philippine local herbal medicine used for diabetes mellitus; bioassay-guided fractionation of the aqueous acetone extract of the leaves afforded three active ellagitannins — lagerstroemin, flosin B, and reginin A — identified by NMR and optical rotation, and these compounds increased glucose uptake of rat adipocytes, which could be responsible for lowering the blood glucose level. This foundational 2002 study (published in Planta Medica) is the key direct experimental evidence for reginin A's activity. It is an in vitro study only, using rat adipocyte cells as a model system.

Earlier work had reported opposing effects of different compounds isolated from L. speciosa leaves on glucose transport (GLUT4) assay: ellagitannins from L. speciosa activated GLUT4, while ellagic acid derivatives showed an inhibitory effect. This finding is important because it indicates that the composition of an extract — specifically the ratio of ellagitannins to ellagic acid derivatives — critically determines net biological activity.

Animal Evidence

As part of continuing research on anti-diabetic nutritional supplements, one study compared the anti-diabetic effects of several extracts from L. speciosa leaves using different manufacturing processes, evaluating their effects on glucose uptake and adipocyte differentiation in 3T3-L1 cells in vitro as well as in alloxan-induced diabetic mice in vivo; extracts were given to mice by gavage at doses of 0.25, 1.0, and 4.0 g/kg body weight once daily for 21 consecutive days. The study evaluated reginin A as part of the ellagitannin-containing fractions rather than as an isolated compound.

Human / Clinical Evidence

No published clinical trial has examined reginin A as an isolated, purified compound in human subjects. Human evidence relates entirely to banaba leaf extracts, of which reginin A is one constituent. The hypoglycemic effects of banaba have been attributed to both corosolic acid as well as ellagitannins; studies have been conducted in various animal models, human subjects, and in vitro systems using water-soluble banaba leaf extracts, corosolic acid, and ellagitannins; corosolic acid has been reported to decrease blood sugar levels within 60 minutes in human subjects.

One notable human crossover study used a proprietary product called Banabamin: twenty-four human subjects with mild type 2 diabetes were given three tablets three times daily, and a 13.5% average decrease in blood glucose levels was reported with no adverse effects observed; however, the constituents in the product responsible for the antidiabetic effect were not determined. The product contained extracts of green tea, green coffee, and Garcinia in addition to banaba, making attribution to any single constituent including reginin A impossible.

In a separate 1-year open-label study: Ikeda et al. conducted a 1-year open-label safety and efficacy study on 15 subjects, administering 100 mg tablets daily of a water-soluble banaba extract; the extract was not standardized, and the constituent(s) responsible for the antidiabetic effects were not determined.

In a study of 12 subjects with fasting blood glucose levels greater than 110 mg/dL given 10 mg of corosolic acid as a banaba extract daily for 2 weeks, consumption of banaba extract reduced fasting and postprandial blood glucose levels by 12%, with no side effects observed during or after the study.

A later randomized, double-blind, placebo-controlled trial examined banaba specifically on metabolic syndrome: a randomized, double-blind, placebo-controlled clinical trial was carried out in 24 patients with diagnosis of metabolic syndrome; 12 patients received banaba (500 mg) twice a day, before breakfast and dinner for 12 weeks, while the remaining 12 patients received placebo.

Evidence strength assessment: The evidence directly attributing biological activity to reginin A itself is limited to a small number of in vitro studies using rat adipocytes. No human clinical trial has isolated or standardized reginin A as a primary intervention. Human evidence relates to whole banaba extracts, which contain multiple bioactive constituents, and the available clinical trials are small, often uncontrolled or not standardized, and insufficient to establish efficacy for any single compound including reginin A.

5.2 Anti-Obesity Activity

Casuarinin and lagerstroemin (closely related C-glycosidic ellagitannins co-occurring with reginin A) were identified as active components in the inhibition of adipocyte differentiation in 3T3-L1 cells. At the whole-extract level, banaba has also been investigated for effects on body weight. Banaba has been used as a functional food because of its diuretic, decongestant, antipyretic, anti-hyperglycemic, and anti-adipogenic activities.

Research on banaba leaf extracts has revealed anti-bacterial, anti-viral, anti-inflammatory, anti-obesity, anti-fibrotic, and anti-diabetic properties. However, as with the glycemic area, no published human data isolates reginin A's contribution to anti-obesity outcomes. All available evidence is either in vitro or at the whole-extract level.

5.3 Antioxidant Activity

The choice of extraction solvent influenced the antioxidant activity of L. speciosa leaves, with ethyl acetate and ethanol extracts showing superior activity compared to methanol and water extracts. As a member of the ellagitannin class, reginin A is expected to contribute to the polyphenolic antioxidant capacity of banaba extracts, though no study has quantified its specific contribution relative to co-occurring compounds. Corosolic acid also exhibits antihyperlipidemic and antioxidant activities.

5.4 Anticancer and Antitumor Activity

Pharmacological research has revealed that the leaves of L. speciosa exhibit a wide range of activities, including antimicrobial, antioxidant, anticancer, antidiabetic, lipid-lowering, anti-inflammatory, pain-relieving, gastrointestinal, cardiovascular, liver-protective, and kidney-protective effects. Other related banaba tannins (PGG) possess additional health-beneficial bioactivities, such as anticancer, anti-inflammation, anti-virus (anti-HIV, anti-SARS), and antioxidant activity. These findings are extrapolated from in vitro and animal data and have not been specifically attributed to reginin A in human studies.

5.5 Kidney and Diuretic Applications

Banaba is also recommended in traditional medicine for kidney and bladder problems as well as hypertension. The tropical plant banaba has been used as a folk medicine for the treatment of diabetes and kidney diseases. No controlled clinical studies have evaluated reginin A specifically for kidney-related endpoints.

6. Body Systems and Health Areas of Association

Endocrine / Metabolic system: Primary area of scientific interest. Reginin A and co-occurring banaba ellagitannins activate GLUT4, promoting cellular glucose uptake in adipocytes and muscle cells, with insulin-receptor-mediated signaling via PI3K.
Cardiovascular system: Banaba constituents appear to involve regulation of lipid metabolism, with research interest in anti-hyperlipidemic effects at the whole-extract level.
Renal / Urinary system: Banaba leaves have been traditionally consumed for treatment of kidney-related diseases, though reginin A's specific renal mechanisms have not been delineated.
Immune / Anti-inflammatory system: Recent studies have shown that Lagerstroemia speciosa has antioxidant, anti-inflammatory, anticancer, anti-obesity, and anti-diabetic activities.
Adipose tissue / Body weight: Anti-adipogenic activity has been demonstrated for related C-glycosidic ellagitannins in cell models.

7. Dosage Forms and Dosages Reported in Studies

Because reginin A is not commercially available in purified form, dosages in published studies pertain to banaba leaf extracts (of which reginin A is a constituent) rather than to reginin A itself. The following reflect dosages reported in identified studies:

In a human study, subjects with elevated fasting blood glucose were given 10 mg of corosolic acid as a banaba extract daily for 2 weeks, resulting in a 12% reduction in fasting and postprandial blood glucose levels.
In a 1-year open-label safety and efficacy study, 15 subjects were administered 100 mg tablets daily of a water-soluble banaba extract.
In a randomized controlled trial, 12 patients received banaba (500 mg) twice a day, before breakfast and dinner for 12 weeks, while the remaining 12 received placebo at the same dosage.
In a murine in vivo study, banaba leaf extracts were given to mice by gavage at doses of 0.25, 1.0, and 4.0 g/kg body weight once daily for 21 consecutive days.

No study in the identified literature reports a dosage for reginin A as an isolated compound in either human or animal studies.

8. Safety Considerations and Interactions

8.1 General Safety Profile of Banaba Extracts

As reginin A is consumed as part of banaba leaf preparations rather than in isolation, its safety profile is inseparable from that of the broader extract. No adverse effects have been observed or reported in animal studies or controlled human clinical trials of banaba extracts and corosolic acid.

However, the duration of studied safety is limited. Banaba is possibly safe when used short-term and has been used safely for up to 2 weeks; there is not enough reliable information to know if banaba is safe to use long-term. Side effects reported include dizziness, headache, and upset stomach.

8.2 Hypoglycemia Risk

Given that reginin A and co-occurring ellagitannins activate GLUT4 to lower blood glucose, and that banaba extracts have demonstrated measurable hypoglycemic activity in human subjects, there is a theoretical and practically relevant risk of excessive blood glucose lowering. This risk is heightened when banaba preparations are combined with pharmaceutical antidiabetic agents. The beneficial effects of banaba with respect to glucose metabolism appear to involve enhanced cellular uptake of glucose, impaired hydrolysis of sucrose and starches, and decreased gluconeogenesis. Multiple simultaneous glucose-lowering mechanisms increase the potential for additive or synergistic hypoglycemia.

8.3 Potential Drug Interactions

The beneficial effects of banaba and corosolic acid involving enhanced cellular uptake of glucose, impaired hydrolysis of sucrose and starches, decreased gluconeogenesis, and regulation of lipid metabolism may be mediated by PPAR, MAP kinase, NF-κB, and other signal transduction factors. The involvement of these broad signaling pathways raises the possibility of interactions with pharmaceutical agents targeting the same pathways (e.g., PPAR-gamma agonists such as thiazolidinediones). The literature identified does not document specific pharmacokinetic drug interaction studies for reginin A.

8.4 Variability in Ellagitannin Content Across Preparations

A notable safety and efficacy concern arises from the manufacturing-dependent variability in reginin A content. Ellagitannins from L. speciosa activated GLUT4, while ellagic acid derivatives showed an inhibitory effect, meaning that preparations with a high ellagic acid content (a hydrolysis product of ellagitannins that accumulates during processing) could counteract the glucose-lowering effects associated with reginin A. The net metabolic effect of any given banaba preparation therefore depends critically on the ratio of intact ellagitannins to ellagic acid derivatives — a ratio influenced by drying method, extraction solvent, and storage conditions. It is not clear if banaba plants grown in different countries are equally effective in the treatment of diabetes, suggesting that geographical and agricultural variables further influence ellagitannin composition.

8.5 Pregnancy, Lactation, and Special Populations

The identified literature does not include controlled studies of banaba or its ellagitannin constituents — including reginin A — in pregnant or lactating individuals. No safety data for these populations was located in the peer-reviewed sources searched.

8.6 Tannin-Related Considerations

As a hydrolysable tannin, reginin A shares the general property of tannins to complex with dietary proteins and minerals. The biological activities of ellagitannins are caused by molecular bonding between the ellagitannin and other compounds, especially proteins, that form complex compounds and change physiological processes in cells or tissues. This protein-binding capacity is relevant to absorption and could theoretically reduce the bioavailability of co-administered amino acids or minerals when consumed with food, though no specific study quantifying this effect for reginin A was identified.

9. Current Research Landscape and Evidence Gaps

In the 1990s, the popularity of banaba herbal medicine began to attract the attention of scientists worldwide; since then, researchers have conducted numerous in vitro and in vivo studies consistently confirming the antidiabetic activity of banaba, and scientists have identified different components responsible for its activity.

From the known studies, tannin molecules are responsible for the insulin-like glucose transport stimulatory activity of banaba extract. Gallotannins such as PGG appear to be more potent and efficacious than ellagitannins such as lagerstroemin. This comparative potency data implies that reginin A, while contributing to overall activity, may not be the most pharmacologically dominant tannin in the extract.

The key evidence gaps for reginin A specifically include: (1) no published pharmacokinetic data — bioavailability, metabolism, and elimination in humans are unknown; (2) no human clinical trial using reginin A as a standardized or isolated compound; (3) no established safe or effective dose range; (4) no systematic review or meta-analysis specifically addressing reginin A; and (5) no data on long-term safety. These gaps reflect the compound's status as a co-constituent of a complex botanical extract rather than as a independently studied nutraceutical agent.

References

Health Conditions

Health conditions that Reginin A may help support.

No conditions available.

Body Systems

Body systems that Reginin A may help support.

No body systems available.