Traditional Herbal Medicines for Diabetes Used in Europe and Asia: Remedies From Croatia and Sri Lanka.

Diabetes is a global pandemic where alternative means of combating the disease have been the focus of research in recent years. Herbal remedies for diabetes have proven to be a valuable alternative therapy given the fact that many of the existing synthetic drugs are incapable of curbing the disease progression. This review article serves as an appraisal of highlighting the variety and diversity of herbal remedies that are present around the world by looking at only 2 countries-Croatia and Sri Lanka-located in Europe and Asia, respectively. The following herbs were selected for review: from Croatia: (1) Cichorium intybus, (2) Olea europaea, (3) Taraxacum campylodes, (4) Urtica dioica, and (5) Vaccinium myrtillus; and from Sri Lanka: (1) Acacia catechu, (2) Allium sativum, (3) Aloe vera, (4) Cinnamomum zeylanicum, (5) Gymnema sylvestre, and (6) Zingiber officinale. The botanical origins, bioactive compounds, evidence-based studies on antidiabetic properties, as well as uses and applications of these herbs in various ailments, are included herein. A plethora of scientific evidence on the antidiabetic potency of these herbs exists to date, through which it is apparent that they could be promoted as alternative therapies for diabetes.

Forestalling the Epidemics of Parkinson's Disease Through Plant-Based Remedies.

Parkinson's disease (PD) as the second leading neurodegenerative disease, imposes a heavy burden among individuals as well as economies worldwide. The main characteristics of PD is a progressive loss of dopaminergic neurons resulting in the loss of motor function, the occurrence of non-motor symptoms, and cognitive decline. Similar to many other chronic diseases, complementary and alternative therapies (CAT) are very popular for the treatment of this disease. This review evaluates six plants, three each from European and Asian traditional medicinal systems: (1) Atropa belladonna, (2) Hyoscyamus niger, (3) Lepidium meyenii, (4) Aspargus racemosus, (5) Mucuna pruriens L., and (6) Gingko biloba. Atropa belladonna, and Hyoscyamus niger in particular, are better known for their poisonous and narcotic effects than as potentially effective plants for the treatment of neurodegenerative diseases. Ginkgo biloba is one of the most widely cultured plants in Traditional Chinese Medicine with high antioxidant potential which contributes to its neuroprotective/ anti-apoptotic activity. The bioactive compounds, anti-neurodegenerative effects and other neuroprotective effects of all six plants are discussed herein.

Evaluation of physicochemical properties and antioxidant activities of kombucha "Tea Fungus" during extended periods of fermentation.

Kombucha fermentation is traditionally carried out by inoculating a previously grown tea fungal mat into a freshly prepared tea broth and incubating under aerobic conditions for 7-10 days. In this study, four kombucha beverages were prepared by placing the tea fungal mats in sugared Sri Lankan black tea at varying concentrations for a period of 8 weeks. The antioxidant activities, physicochemical, and qualitative properties were monitored prior to the commencement of the fermentation process, one day after the inoculation with the microorganisms and subsequently on a weekly basis. All samples displayed a statistically significant decrease (p < .05) in the antioxidant activity at the end of 8 weeks, which was indicative of the decreasing functional properties of the beverage. The physicochemical properties indicated increased acidity and turbidity, which might decrease consumer appeal of the fermented beverage. Further studies are necessary to test the accumulation of organic acids, nucleic acids, and toxicity of kombucha on human organs following the extended period of fermentation.

Antidiabetic Effects of Aronia melanocarpa and Its Other Therapeutic Properties.

Diabetes is a global pandemic which warrants urgent attention due to its rising prevalence and economic burden. Thus, many alternative therapies are being researched for antidiabetic properties, given the inefficacy of current medicinal treatments. From this perspective, Aronia melanocarpa or black chokeberry has been investigated for its therapeutic properties in many studies, especially for its ability to combat hyperglycemia-induced oxidative stress and the macrovascular complications of diabetes including cardiovascular disease. Though A. melanocarpa is native to the eastern areas of North America, it has been planted extensively in Europe and Asia as well. Several in vivo studies have displayed the antioxidant properties of A. melanocarpa berry juice and plant extract in rat models where oxidative stress markers were observed to have significant reductions. Some of the potent bioactive compounds present in the fruits and other parts of the plant were identified as (-)-epicatechin, chlorogenic acid, neochlorogenic acid, and cyanidin-3-galactoside. Overall, A. melanocarpa could be considered a good source of antioxidants which is effective in combating hyperglycemia-induced oxidative stress.

Antidiabetic Properties, Bioactive Constituents, and Other Therapeutic Effects of Scoparia dulcis.

This review discusses the antidiabetic activities of Scoparia dulcis as well as its antioxidant and anti-inflammatory properties in relation to the diabetes and its complications. Ethnomedical applications of the herb have been identified as treatment for jaundice, stomach problems, skin disease, fever, and kidney stones, reproductory issues, and piles. Evidence has been demonstrated through scientific studies as to the antidiabetic effects of crude extracts of S. dulcis as well as its bioactive constituents. The primary mechanisms of action of antidiabetic activity of the plant and its bioactive constituents are through α-glucosidase inhibition, curbing of PPAR-γ and increased secretion of insulin. Scoparic acid A, scoparic acid D, scutellarein, apigenin, luteolin, coixol, and glutinol are some of the compounds which have been identified as responsible for these mechanisms of action. S. dulcis has also been shown to exhibit analgesic, antimalarial, hepatoprotective, sedative, hypnotic, antiulcer, antisickling, and antimicrobial activities. Given this evidence, it may be concluded that S. dulcis could be promoted among the masses as an alternative and complementary therapy for diabetes, provided further scientific studies on the toxicological and pharmacological aspects are carried out through either in vivo or clinical means.

Application of the Kombucha 'tea fungus' for the enhancement of antioxidant and starch hydrolase inhibitory properties of ten herbal teas.

Ten herbal teas (Acacia arabica, Aegle marmelos flower, A. marmelos root bark, Aerva lanata, Asteracantha longifolia, Cassia auriculata, Hemidesmus indicus, Hordeum vulgare, Phyllanthus emblica, Tinospora cordifolia) were fermented with the Kombucha 'tea fungus'. The pH values of the fermented beverages ranged from 4.0 to 6.0 by day 7, while the titratable acidity ranged from 2.5 to 5.0g/mL (P<0.05). Gallic acid had statistically significantly increased (P<0.05) in almost all the samples by day 7. The Oxygen radical absorbance capacity assay indicated 5 of the Kombucha beverages to have statistically significant increases (P<0.05) by day 7. The α-amylase inhibitory activities ranged from 52.5 to 67.2µg/mL in terms of IC50 values following fermentation, while the α-glucosidase inhibitory activities ranged from 95.2 to 196.1µg/mL. In conclusion, an enhancement of the antioxidant and starch hydrolase inhibitory potential of the herbal teas was observed by adding the tea fungus.

The Antioxidant and Starch Hydrolase Inhibitory Activity of Ten Spices in an In Vitro Model of Digestion: Bioaccessibility of Anthocyanins and Carotenoids.

The antioxidant and starch hydrolase inhibitory activities of cardamom, cloves, coriander, cumin seeds, curry leaves, fenugreek, mustard seeds, nutmeg, sweet cumin, and star anise extracts were investigated in an in vitro model of digestion mimicking the gastric and duodenal conditions. The total phenolic contents in all spice extracts had statistically significantly (P < 0.05) increased following both gastric and duodenal digestion. This was also in correlation with the antioxidant assays quantifying the water-soluble antioxidant capacity of the extracts. The lipophilic Oxygen Radical Absorbance Capacity assay did not indicate a statistically significant change in the values during any of the digestion phases. Statistically significant (P < 0.05) reductions in the anthocyanin contents were observed during the digestion phases in contrast to the carotenoid contents. With the exception of the cumin seed extract, none of the spice extracts showed statistically significant changes in the initial starch hydrolase enzyme inhibitory values prior to gastric and duodenal digestion. In conclusion, this study was able to prove that the 10 spices were a significant source of total phenolics, antioxidant, and starch hydrolase inhibitory activities.

Free radical scavenging ability of Aspalathus linearis in two in vitro models of diabetes and cancer.

The free radical scavenging activity of Aspalathus linearis (Rooibos tea) and its effect on reactive oxygen species (ROS), catalase (CAT), and superoxide dismutase (SOD) were investigated in two in vitro disease models of cancer and diabetes. Although the antioxidant activity of this tea has been reported in several studies, its effects in disease models of ROS-induced oxidative stress have not been systematically evaluated to date. The oxygen radical absorbance capacity (ORAC) assay was used in this study to quantify the antioxidant capacity of the extract, whereas the ROS scavenging ability in hyperglycemia-induced human umbilical vein endothelial cells (HUVECs) and HeLa cells were investigated. The CAT and SOD assays were also carried out in the two disease models in order to evaluate the effect of the extract in the stimulation of these two enzyme activities. The extract was observed to have reduced ROS in a dose-dependent manner in both HUVECs and HeLa cells. The stimulation of the CAT and SOD enzyme activities were observed to be dose-dependent as well. The high ORAC value of the extract indicated the presence of antioxidant compounds which could directly quench ROS, whereby this mechanism of action could be hypothesized to have been further complemented through the stimulation of CAT and SOD. Overall, the Aspalathus linearis extract was observed to have increased the CAT and SOD activities in two in vitro disease models of cancer and hyperglycemia. Given the correlation between the ORAC values, the increases in CAT and SOD activities and the reduction in ROS in a dose-dependent manner, it could be hypothesized that the extract had a significant therapeutic potential for either the prevention of the onset of the two diseases or their progression because ROS has been identified as their root causes.

Evaluation of the total antioxidant capacity, polyphenol contents and starch hydrolase inhibitory activity of ten edible plants in an in vitro model of digestion.

The total phenolics contents, total antioxidant capacity (TAC) and starch hydrolase inhibitory activity of the aqueous extracts of 10 edible plants and the stability of these parameters after the gastric and duodenal digestion in an in vitro model was investigated. The TAC was evaluated using the oxygen radical absorbance capacity (ORAC) assay, ferric reducing antioxidant power (FRAP) and 2, 2-diphenyl-1-picrylhydrazyl (DPPH•) and 2, 2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•+) radical scavenging assays. Characterization and quantification of five polyphenol compounds which were previously identified to be present in all the selected plants were carried out. None of the extracts showed a decrease in the total phenolics content or the ORAC and FRAP values following digestion. None of the quantified phenolic compounds had decreased during any of the digestion phases - an observation which was deemed as beneficial in terms of therapeutic properties. Overall, the parameters analyzed were relatively stable throughout the digestive process in all the extracts.

An appraisal of eighteen commonly consumed edible plants as functional food based on their antioxidant and starch hydrolase inhibitory activities.

BACKGROUND: Eighteen edible plants were assessed for their antioxidant potential based on oxygen radical absorbance capacity (ORAC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, total phenolics, vitamin C content and various lipophilic antioxidants. The inhibitory activities of the plant extracts against the enzymatic activities of α-amylase and α-glucosidase were also evaluated. RESULTS: The antioxidant and starch hydrolase activities of the plants varied widely across a single batch of analysis. The ORAC and DPPH radical scavenging EC50 values varied between 298 and 1984 Trolox equivalents g(-1) fresh weight and between 91 and 533 mg kg(-1) fresh weight, respectively. The total phenolics and vitamin C contents varied between 32 and 125 mg gallic acid equivalents g(-1) fresh weight and between 96 and 285 µg g(-1) fresh weight, respectively. All the plants contained neoxanthin, violaxanthin, and α- and ß-carotene in varying amounts. Coccinia grandis, Asparagus racemosus, Costus speciosus, Amaranthus viridis and Annona muricata displayed the highest inhibitory activities against starch hydrolases. They were the most efficient against the breakdown of seven starches exposed to the two enzymes as well. CONCLUSIONS: Overall, the edible plants were observed to display a high antioxidant potential with starch hydrolase inhibitory properties, which were beneficial in their being recognized as functional food.

The classification of sri lankan medicinal herbs: an extensive comparison of the antioxidant activities.

Sri Lanka has variety of herbs whose effectiveness has been proven across many generations. These herbs are classified into two groups - 'heating' and 'cooling', based on the physiological reactions upon consumption. Application-wise, the 'cooling' herbs are administered to patients contracted with diabetes, imbalances in the lipid profile, or even cancer. However, this classification has been misunderstood due to inconsistent interpretations and lack of scientific reasoning. This study systematically determines the rationale behind this classification, by specifically evaluating the antioxidant activity of 18 herbs - nine herbs from each category. The oxygen radical absorbance capacities, DPPH radical scavenging activities, and the total phenolic contents are analyzed here. The 'heating' herbs have a comparatively lower antioxidant potential than the 'cooling' herbs. The total phenolic contents correlate with the antioxidant values. It can be hypothesized that the high antioxidant potential of the 'cooling' herbs may have been responsible for the containment of the diseases mentioned previously.

Baicalin upregulates the genetic expression of antioxidant enzymes in Type-2 diabetic Goto-Kakizaki rats.

AIM: The primary purpose of this study was to characterize and investigate the antioxidant and anti-diabetic activities of the flavonoid baicalin in type 2 diabetic Goto-Kakizaki rats. MAIN METHODS: Four groups of Goto-Kakizaki rats (n=6) were subjected to the following oral treatments for 30 days: (1) metformin - 500 mg/kg (2) baicalin - 120 mg/kg (3) metformin 500 mg/kg and baicalin - 120 mg/kg (4) vehicle treated diabetic controls receiving distilled water. The plasma glucose, triglyceride, total cholesterol, lipid peroxide and protein carbonyl contents were measured on a weekly basis. Following the completion of the treatment, the rats were sacrificed and their blood, heart, pancreatic and hepatic tissues were collected for analysis. The antioxidant enzyme activities as well as their expression were quantified using Western Blot, microarray and RT-PCR. KEY FINDINGS: The respective analyses showed that the baicalin- and the metformin and baicalin-treated groups had statistically significant increases (p <0.05) in the activity and expression of the antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) compared with vehicle- and metformin-treated groups. Further complementing the antioxidant enzyme activity increases, the oxidative stress markers of plasma lipid peroxide and protein carbonyl contents were reduced in these groups as well. These treatment groups also had reduced plasma total cholesterol and triglyceride levels compared with vehicle-treated and metformin-treated groups (p <0.05). SIGNIFICANCE: Baicalin was an efficient antioxidant in reducing hyperglycemia-induced oxidative stress through the increased expression of antioxidant enzyme activities. It was also an efficient anti-hypertriglyceridemic as well as anti-hypercholesterolemic agent compared with metformin.

Baicalin reduces mitochondrial damage in streptozotocin-induced diabetic Wistar rats.

BACKGROUND: Hyperglycemia-induced superoxide production in the mitochondria is known to be the primary cause of diabetic micro- and macro-vascular complications and mitochondrial membranal damage. This study in streptozotocin-induced diabetic Wistar rats investigated the anti-hyperglycemic and mitochondrial membrane protection effects of baicalin, a flavonoid known for its radical scavenging activity. METHODS: The following oral treatments were given to diabetic rats for 30 days: (1) metformin 500 mg/kg, (2) baicalin 120 mg/kg, and (3) metformin 500 mg/kg & baicalin 120 mg/kg, with vehicle-treated diabetic and non-diabetic groups serving as controls. RESULTS: Transmission electron microscopy imaging of pancreatic beta-cells revealed loss of integrity of the inner membrane of the mitochondria in the diabetic rats, which was not observed in the baicalin-treated group. In addition, baicalin and the combined treatment of metformin and baicalin had significantly reduced (p < 0.05) the number of mitochondria with a damaged membrane compared to the diabetic control as well as the metformin-treated group in the hepatic tissues. Baicalin had also increased the plasma leptin content (p < 0.05) versus the diabetic control, which in turn had effected the total expression of hepatic mitochondria per cell indicating its effects in SIRT1 activity. The increase in mitochondrial number was further complemented with similar trends in the hepatic citrate synthase activity. CONCLUSIONS: Baicalin had reduced the hyperglycemia-induced mitochondrial membrane damage, as well as enhanced the effects of metformin, as was observed in the results from the metformin and baicalin treated groups.

Baicalin improves antioxidant status of streptozotocin-induced diabetic Wistar rats.

This study investigated the antioxidant and antidiabetic effects of baicalin, as well as its effects in combination with the antidiabetic drug metformin. Three groups of streptozotocin-induced diabetic rats were given the following treatments for 30 days: (1) 500 mg/kg metformin; (2) 120 mg/kg baicalin; (3) 500 mg/kg metformin + 120 mg/kg baicalin. In addition, vehicle-treated diabetic and nondiabetic controls were used in the experiment. The rats treated with baicalin and metformin + baicalin had significantly elevated (p < 0.05) hepatic activities of superoxide dismutase, catalase, and glutathione peroxidase compared with the vehicle- and metformin-treated groups. Plasma and hepatic lipid peroxide concentrations of the baicalin- and baicalin + metformin-treated groups were significantly reduced (p < 0.05). In addition, baicalin significantly reduced plasma and hepatic triglycerides and cholesterol levels. The study thus showed that baicalin mitigated oxidative stress as well as enhanced the antidiabetic effect of metformin by improving the antioxidant status.

Characterization of the anti-diabetic and antioxidant effects of rehmannia glutinosa in streptozotocin-induced diabetic Wistar rats.

This study investigated the effects of Rehmannia glutinosa individually as well as in combination with the oral hypoglycemic agent, metformin in streptozotocin (STZ)-induced diabetic Wistar rats. R. glutinosa ethanolic extract was prepared and the constituents were characterized using fractionation by column chromatography, followed by high performance liquid chromatography-mass spectrometry. STZ (65 mg/kg) was injected intraperitoneally to induce diabetes in Wistar rats. The diabetic rats were divided into the following groups (each n = 6) and received the respective treatments for 30 days: (1) metformin (500 mg/kg), (2) R. glutinosa (200 mg/kg), (3) metformin (500 mg/kg) and R. glutinosa (200 mg/kg) and (4) diabetic control (DC). A reduction in plasma glucose levels caused by the herb was not as significant as metformin compared to the diabetic control (p < 0.05). However, R. glutinosa-treated group showed reductions in plasma C-reactive protein (CRP) levels compared to the diabetic controls (p < 0.05) as well as metformin-treated group (p < 0.05). An enhanced reduction in CRP concentration was observed in the group receiving both herb and metformin compared to metformin-treated group (p < 0.05). Reduction in CRP levels suggests an anti-inflammatory activity of the herb.

Scutellaria baicalensis enhances the anti-diabetic activity of metformin in streptozotocin-induced diabetic Wistar rats.

Oxidative stress is the root cause of diabetic macro- and microvascular complications. Biochemical and epidemiological studies indicate that current treatments for diabetes do not reduce risks of developing complications, suggesting their inability to alleviate the levels of oxidative stress. This study in streptozotocin (STZ)-induced diabetic rats was carried out to investigate the effect of combining the antidiabetic drug, metformin, with an ethanolic extract of Scutellaria baicalensis, a plant whose root is known for its radical scavenging activity. Three groups of STZ-induced diabetic rats were given the following treatments for 30 days: (1) metformin 500 mg/kg, (2) S. baicalensis 400 mg/kg, (3) metformin 500 mg/kg + S. baicalensis extract 400 mg/kg. In addition, vehicle-treated diabetic and nondiabetic controls were used in the experiment. The rats treated with S. baicalensis and metformin + S. baicalensis had elevated hepatic activities of the antioxidant enzymes--superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) compared to the vehicle- and metformin-treated diabetic groups (p < 0.05). Plasma and hepatic lipid peroxide concentrations in the herb-treated and herb + metformin-treated groups were also significantly reduced (p < 0.05). In addition, the combined treatment caused significant elevations of plasma and pancreatic insulin levels and reductions of plasma and hepatic triglycerides (TG) and cholesterol levels. The study thus showed that S. baicalensis enhanced the antidiabetic effect of metformin in STZ-induced diabetic rats by improving the antioxidant status. It also increased pancreatic insulin content as well as improved the lipid profile in these rats.