UP165, A Standardized Corn Leaf Extract for Improving Sleep Quality and Mood State.

UP165, a standardized Zea mays (corn) leaf extract, was evaluated for its effect on sleep quality and overall well-being in a double-blind, placebo-controlled clinical trial, administered orally at 250 and 500 mg/day. Participants (n = 45) (age range 19-73) consumed the supplement or placebo ∼60 minutes before bedtime daily for 4 weeks. Measurements that were evaluated were as follows: daily sleep quality, as monitored by a fitness tracker; the Pittsburgh Sleep Quality Index (PSQI) for sleep quality and efficiency; salivary cortisol levels for stress; and Profile of Mood States (POMS) to assess general well-being. Participants who received UP165 showed a statistically significant and dose-correlated reduction in salivary cortisol (up to 36%); an increase in deep sleep time (up to 30 minutes); increased total sleep time (up to 10%); an improvement in sleep quality (up to 49%), and an enhanced POMS (36-58%). Participants in the UP165 group showed a sevenfold increase in deep sleep time and a 10-fold increase in PSQI sleep quality improvement compared to placebo. Collectively, UP165 is a safe nutritional supplement clinically proven for a 24-hour support with better quality and efficiency of sleep at night and an improved mood state and overall well-being during the day. The clinical study has been ISRCTN registered with study ID ISRCTN68282897.

Antinociceptive and Anti-Inflammatory Properties of Cannabidiol Alone and in Combination with Standardized Bioflavonoid Composition.

Symptom-alleviating therapies for osteoarthritis (OA) management are inadequate. Long-term application of first-line treatments, such as nonsteroidal anti-inflammatory drugs, is limited due to associated side effects. We believe that a combination of traditionally used botanical extracts, which have diverse active components that target multiple inflammatory pathways, may provide a safe and efficacious alternative to address the multifactorial nature of OA. Recently, cannabidiol (CBD), the major nonpsychoactive component of the hemp plant, has gained renewed global attention for its pharmacological actions. It has shown promise in reducing pain and inflammation in preclinical models of arthritis. In this study, widely employed inflammatory and noninflammatory animal pain models, such as the hot plate test, visceral pain model (writhing test), and carrageenan-induced rat paw edema model, were utilized to evaluate the antinociceptive and anti-inflammatory activity of CBD alone and in combination with standardized bioflavonoid compositions. CBD was tested at 5, 10, 20, and 40 mg/kg orally and at 5% topically. Administered alone, CBD produced dose-correlated, statistically significant pain inhibition in all the models. Enhanced performance in pain and inflammation reduction was observed when CBD was orally administered in complex with the bioflavonoid compositions. Data from this study show that for clinically meaningful efficacy against OA, CBD may have to be delivered in higher dosage or formulated with other medicinal plants with similar activities.

Morus alba, a Medicinal Plant for Appetite Suppression and Weight Loss.

The prevalence of obesity is expanding rapidly worldwide, making the disease a global burden with limited treatment options. The current obesity drug development trends suggest the possibility of reducing weight and reverse metabolic disturbances of obesity by controlling appetite. In this study, we screened more than 8000 plants from our plant library for the cannabinoid (CB1) receptor antagonists and identified Morus alba as a lead medicinal plant. Kuwanon G and Albanin G were isolated and identified from root-barks of Morus alba with 92% and 96% CB1 receptor ligand binding inhibitory activity, respectively. The bioflavonoid standardized extract was tested in the acute food intake study in rats at oral doses of 250 and 500 mg/kg for its appetite suppression activity. Diet-induced obesity in the C57BL/6J mice was used to evaluate the long-term food intake reduction activity and effect on the weight loss administered orally at 250 and 500 mg/kg for 7 weeks. Statistically significant and dose-dependent reduction in food intake was observed in both acute and long-term studies for the extract. Food intake reductions of 58.6% and 44.8% at 250 mg/kg and 50.1% and 44.3% at 500 mg/kg were observed at 1 and 2 h postfood provision, respectively. A 20% reduction in daily calorie intake was observed in the long-term study. Obese mice treated with the high dose of Morus root-bark extract showed 10.4 g (22.5%) and 7.1 g (16.5%) loss in body weight compared with the vehicle-treated obese animals (at week 7) and baseline, respectively. Statistically significant reductions in biochemical markers and visceral fat deposit were also observed. These results demonstrated that Morus alba extracts enriched in Kuwanon G, and Albanin G could be used alone to control appetite, manage body weight, and improve metabolic syndromes.

UP1306: A Composition Containing Standardized Extracts of Acacia catechu and Morus alba for Arthritis Management.

Osteoarthritis (OA) is characterized by progressive articular cartilage degradation. Although there have been significant advances in OA management, to date, there are no effective treatment options to modify progression of the disease. We believe these unmet needs could be bridged by nutrients from natural products. Collagen induced arthritis in rats was developed and utilized to evaluate anti-inflammatory and cartilage protection activity of orally administered botanical composition, UP1306 (50 mg/kg) and Methotrexate (75 µg/kg) daily for three weeks. Objective arthritis severity markers, urine, synovial lavage, and serum were collected. At necropsy, the hock joint from each rat was collected for histopathology analysis. Urinary cartilage degradation marker (CTX-II), pro-inflammatory cytokines (tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), and IL-6), and proteases (Matrix Metallopeptidase 3 (MMP3) and 13) were measured. Rats treated with UP1306 showed statistically significant improvements in arthritis severity markers, including uCTX-II (91.4% vs. collagen-induced arthritis (CIA)), serum IL-1ß, TNF-α, and IL-6 levels as well as synovial MMP-13. The histopathology data were also well aligned with the severity score of arthritis for both UP1306 and Methotrexate. UP1306, a botanical composition that contains a standardized blend of extracts from the heartwood of Acacia catechu and the root bark of Morus alba, could potentially be considered as a dietary supplement product for the management of arthritis.

Evaluation of Natural Product Compositions for Appetite Suppression.

A change in homeostasis between food intake and energy expenditure is the hallmark of obesity. Many plant-based weight-management products are available in dietary supplement markets with no direct efficacy comparison. In this in vivo acute feed intake study in rats, the appetite suppression efficacy of well-known natural ingredients in the weight-loss market were evaluated. We tested pure caffeine, potato skin extract, Cissus quadrangularis extract, Garcinia cambogia extract, Crocus sativus extract, raspberry ketone isolated from Rubus idaeus, one commercial product (Appetrex), and one novel composition (UP601). Rats treated with potato skin extract, Crocus sativus bulb extract, and Cissus quadrangularis extracts showed statistically significant reduction in food consumption only at the 2-hour timepoint with 44.9%, 34.1%, and 44.3% reductions, respectively, after food provision at an equivalent human dosage of 2 g, 10 g, and 10 g, respectively. Garcinia cambogia fruit extract and raspberry ketone from Rubus idaeus showed statistically significant reduction in food consumption only at the 1-hour timepoint with 33.7% and 79.4% reductions, respectively, after food provision at an equivalent human dosage of 8 g and 5 g, respectively. UP601 and Appetrex were compared at 230 mg/kg. While 88.5%, 73.8%, and 63.1% reductions in food intake were observed for the UP601 treatment group, 64.2%, 27.5%, and 34.7% reductions in food intake were observed for rats treated with Appetrex at 1 h, 2 h, and 4 h after food provision. The composition UP601 demonstrated superior activity in food intake compared to any of the dietary supplements marketed for appetite suppression tested in this study.

Repeated dose 28-day oral toxicity study of a botanical composition composed of Morus alba and Acacia catechu in rats.

Patients with osteoarthritis experience debilitating pain and loss of joint function that requires chronic treatment. While nonsteroidal anti-inflammatory drugs (NSAIDs) have been effective for temporary symptomatic relief, their long term usage has been limited by their associated side-effects. UP1306, a standardized novel composition from the extracts of root barks of Morus alba and the heartwoods of Acacia catechu, has been used in over the counter joint care dietary supplements as a safer alternative. These two medicinal plants have long track records of safe human consumption. Here we evaluated the potential adverse effects of orally administered UP1306 in Sprague Dawley rats following a 28-day repeated oral dose toxicity study. UP1306 at doses of 500, 1000 and 2000 mg/kg/day were administered orally to rats for 4 weeks. A 2-week recovery group from the high dose (2000 mg/kg) and vehicle treated groups were included. No morbidity or mortality was observed for the duration of the study. No significant differences between groups in body weights, food consumption, hematology, clinical chemistry, organ weights, gross pathology and histopathology were documented. Minor aberrations from the normal observed for the main groups were considered reversible as they were not evident in the recovery period. In conclusion, the no-observed-adverse-effect-level (NOAEL) of UP1306 was considered to be the highest dose tested, 2000 mg/kg/day, both for male and female rats.

Cartilage Protection and Analgesic Activity of a Botanical Composition Comprised of Morus alba, Scutellaria baicalensis, and Acacia catechu.

Although there have been augmented advances in drug discovery, current OA management is inadequate due to the lack of successful therapies proven to be effective in modifying disease progression. For some, the risk outweighs the benefit. As a result, there is a desperate need for safe and efficacious natural alternatives. Here we evaluated a composition from Morus alba, Scutellaria baicalensis, and Acacia catechu in maintaining joint structural integrity and alleviating OA associated symptoms in monoiodoacetate- (MIA-) induced rat OA disease model. Study lasted for 6 weeks. 59.6%, 64.6%, 70.7%, 69.9%, and 70.3% reductions in pain sensitivity were observed for rats treated with the composition from week 1 to week 5, respectively. Statistically significant improvements in articular cartilage matrix integrity (maintained at 57.1% versus MIA + vehicle treated rats) were shown from the modified total Mankin score for animals treated with the composition. The composition showed a statistically significant reduction in uCTX-II level (54.1% reductions). The merit of combining these botanicals was also demonstrated in their synergistic analgesic activity. Therefore, the standardized blend of Morus alba, Scutellaria baicalensis, and Acacia catechu could potentially be considered as an alternative remedy from natural sources for the management of OA and/or its associated symptoms.

A Botanical Composition from Morus alba, Ilex paraguariensis, and Rosmarinus officinalis for Body Weight Management.

Obesity is the largest and fastest growing public health catastrophe in the world affecting both adults and children with a prevalence impacting more than one-third of United States (US) adult population. Although the long-term solution lies in lifestyle changes in the form of dieting and exercise, intervention is required for those who are already obese. Unfortunately, treatment options remain quite limited due to associated side effects of conventional therapeutics. As a natural alternative, in this study we describe the beneficial effect of a standardized composition (UP603) comprised of extracts from Morus alba, Ilex paraguariensis, and Rosmarinus officinalis in improving metabolic disorders in high fat diet (HFD) and high fat & high fructose diet (HFFD) induced obese C57BL/6J mice. Mice treated with UP603 showed dose-correlated decrease in body weight gains compared to vehicle treated HFFD group. Following 7 weeks of treatment, the changes in body weight gains from baseline were found as 6.4%, 27.3%, 2.0%, 3.1%, 0.4%, and -2.9% for normal control diet, HFFD, Orlistat, 450, 650, and 850 mg/kg UP603 treated animals, respectively. Reductions of 7.9-21.1% in total cholesterol, 25.4-44.6% in triglyceride, and 22.5-38.2% in low-density lipoprotein were observed for mice treated with 450-850 mg/kg of UP603. In a dual energy X-ray absorptiometry scan, percentage body fat of 18.9%, 47.8%, 46.1%, and 40.4% were found for mice treated with normal control, HFD, Orlistat, and UP603, respectively. Reductions of 65.5% and 16.4% in insulin and leptin, respectively, and 2.1-fold increase in ghrelin level were also observed for the UP603 group. Statistically significant improvements in nonalcoholic steatohepatitis scores were also observed from liver histology for mice treated with UP603. Hence, UP603, a standardized botanical composition from M. alba, I. paraguariensis, and R. officinalis could potentially be considered as a natural alternative to maintain healthy body weight and to manage metabolic syndrome.

Corrigendum to "Clinical and Preclinical Cognitive Function Improvement after Oral Treatment of a Botanical Composition Composed of Extracts from Scutellaria baicalensis and Acacia catechu".

[This corrects the article DOI: 10.1155/2016/7240802.].

A Botanical Composition Mitigates Cartilage Degradations and Pain Sensitivity in Osteoarthritis Disease Model.

Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive articular cartilage degradation manifested with significant functional impairment in consort with signs and symptoms of inflammation, stiffness, and loss of mobility. Current OA management is inadequate due to the lack of nominal therapies proven to be effective in hampering disease progression where symptomatic therapy focused intervention masks the primary etiology leading to irreversible structural damage. In this study, we describe the effect of UP1306, a composition containing a proprietary blend of two standardized extracts from the heartwood of Acacia catechu and the root bark of Morus alba, in maintaining joint structural integrity and alleviating OA associated symptoms in monosodium-iodoacetate (MIA)-induced rat OA disease model. Data from pain sensitivity, histopathology, and glycosaminoglycan (GAG) level were analyzed. Diclofenac at 10 mg/kg was used as a reference compound. Ex vivo proteoglycan protection model demonstrated 31.5%, 50.0%, and 54.8% inhibitions of proteoglycan degradations from UP1306 at concentrations of 50, 100, and 200 µg/mL, respectively. The merit of combining two bioflavonoid standardized extracts from A. catechu and M. alba was demonstrated in their Ex vivo synergistic proteoglycan protection activity. In the MIA in vivo OA model, administered orally at 500 mg/kg, UP1306 resulted in reductions of 17.5%, 29.0%, 34.4%, 33.5%, and 40.9% through week 1-5 in pain sensitivity, statistically significant improvements in articular cartilage matrix integrity, and minimal subchondral bone damage. Therefore, UP1306 could potentially be considered as an alternative remedy from natural sources for the management of OA and/or its associated symptoms.

UP601, a standardized botanical composition composed of Morus alba, Yerba mate and Magnolia officinalis for weight loss.

BACKGROUND: The prevalence of obesity is surging in an alarming rate all over the world. Pharmaceutical drugs are considered potential adjunctive therapy to lifestyle modification. However, for most, besides being too expensive, their long term usages are hindered by their severe adverse effects. Here we describe the effect of UP601, a standardized blend of extracts from Morus alba, Yerba mate and Magnolia officinalis, in modulating a number of obesity-related phenotypic and biochemical markers in a high-fat high-fructose (HFF)-induced C57BL/6J mouse model of obesity. METHOD: Adipogenesis activity of the composition was assessed in 3T3-L1 cells in vitro. Effects of UP601 on body weight and metabolic markers were evaluated. It was administered at oral doses of 300 mg/kg, 450 mg/kg and 600 mg/kg for 7 weeks. Orlistat (40 mg/kg/day) was used as a positive control. Body compositions of mice were assessed using dual energy X-ray absorptiometry (DEXA). Serum biomarkers were measured for liver function and lipid profiling. Relative organ weights were determined. Histopathological analysis was performed for non-alcoholic steatohepatitis (NASH) scoring. RESULTS: UP601 at 250 µg/ml resulted in 1.8-fold increase in lipolysis. Statistically significant changes in body weight (decreased by 9.1, 19.6 and 25.6% compared to the HFF group at week-7) were observed for mice treated with UP601 at 300, 450 and 600 mg/kg, respectively. Reductions of 9.1, 16.9, and 18.6% in total cholesterol; 45.0, 55.0, 63.6% in triglyceride; 34.8, 37.1 and 41.6% in LDL; 3.2, 21.6 (P = 0.03) and 33.7% (P = 0.005) in serum glucose were observed for UP601 at 300, 450 and 600 mg/kg, respectively. Body fat distribution was found reduced by 31.6 and 17.2% for the 450 mg/kg UP601 and orlistat, respectively, from the DEXA scan analysis. Up to an 89.1% reduction in mesenteric fat deposit was observed for UP601 in relative organ weight. Statistically significant improvements in NASH scores were observed for mice treated with UP601. CONCLUSION: UP601, a standardized botanical composition from Morus alba, Yerba mate and Magnolia officinalis could potentially be used for achieving healthy weight loss and maintenance.

Appetite Suppression and Antiobesity Effect of a Botanical Composition Composed of Morus alba, Yerba mate, and Magnolia officinalis.

Background. Obesity and its comorbidities continue to challenge the world at an alarming rate. Although the long term solution lies on lifestyle changes in the form of dieting and exercising, drug, medical food, or dietary supplement interventions are required for those who are already obese. Here we describe a standardized blend composed of extracts from three medicinal plants: Morus alba, Yerba mate, and Magnolia officinalis for appetite suppression and metabolic disorders management. Method. Extracts were standardized to yield a composition designated as UP601. Appetite suppression activity was tested in acute feed intake rat model. Efficacy was evaluated in C57BL/6J mouse models treated with oral doses of 1.3 g/kg/day for 7 weeks. Orlistat at 40 mg/kg/day was used as a positive control. Body compositions of mice were assessed using a dual energy X-ray absorptiometry (DEXA). ELISA was done for insulin, leptin, and ghrelin level quantitation. Nonalcoholic steatohepatitis (NASH) scoring was conducted. Results. Marked acute hypophagia with 81.8, 75.3, 43.9, and 30.9% reductions in food intake at 2, 4, 6, and 24 hours were observed for UP601. Decreases in body weight gain (21.5% compared to the HFD at weeks 7 and 8.2% compared to baseline) and calorie intake (40.5% for the first week) were observed. 75.9% and 46.8% reductions in insulin and leptin, respectively, 4.2-fold increase in ghrelin level, and reductions of 18.6% in cholesterol and 59% in low-density lipoprotein were documented. A percentage body fat of 18.9%, 47.8%, 46.1%, and 30.4% was found for mice treated with normal control, HFD, Orlistat, and UP601, respectively. 59.3% less mesenteric fat pad and improved NASH scores were observed for UP601. Conclusion. UP601, a standardized botanical composition from Morus alba, Yerba mate, and Magnolia officinalis could be used as a natural alternative for appetite suppression, maintaining healthy body weight and metabolism management.

Analgesic and anti-inflammatory effects of UP1304, a botanical composite containing standardized extracts of Curcuma longa and Morus alba.

OBJECTIVE: Though the initial etiologies of arthritis are multifactorial, clinically, patients share the prime complaints of the disease, pain. Here the authors assessed the analgesic and anti-inflammatory effects of UP1304, a composite that contains a standardized blend of extracts from the rhizome of Curcuma longa and the root bark of Morus alba, on rats with carrageenan-induced paw edema. METHODS: A plant library was screened for bradykinin receptor antagonists. In vivo, the anti-inflammatory and analgesic effects of the standardized composite, UP1304, were evaluated in rats with carrageenan-induced paw edema using oral dose ranges of 100-400 mg/kg. Ibuprofen, at a dose of 200 mg/kg, was used as a reference compound. In vitro, cyclooxygenase (COX) and lipoxygenase (LOX) inhibition assays were performed to evaluate the degree of inflammation. RESULTS: Statistically significant improvements in pain resistance and paw edema suppression were observed in animals treated with UP1304, when compared to vehicle-treated rats. Results from the highest dose of UP1304 (400 mg/kg) were similar to those achieved by ibuprofen treatment at 200 mg/kg. In vitro, UP1304 showed dose-dependent inhibition of the enzymatic activities of COX and LOX. A half-maximal inhibitory concentration of 9.6 µg/mL for bradykinin B1 inhibition was calculated for the organic extract of C. longa. Curcumin showed Ki values of 2.73 and 58 µg/mL for bradykinin receptors B1 and B2, respectively. CONCLUSION: Data presented here suggest that UP1304, analgesic and anti-inflammatory agent of botanical origin, acted as a bradykinin receptor B1 and B2 antagonist, and inhibited COX and LOX enzyme activities. This compound should be considered for the management of symptoms associated with arthritis.

Clinical and Preclinical Cognitive Function Improvement after Oral Treatment of a Botanical Composition Composed of Extracts from Scutellaria baicalensis and Acacia catechu.

Dementia and cognitive impairment have become the major concerns worldwide due to a significantly aging population, increasing life span and lack of effective pharmacotherapy. In light of limited pharmaceutical drug choices and the socioeconomic implications of these conditions, the search for safe and effective alternatives from natural sources has gained many attractions within the medical food and dietary supplement industry. Two polyphenol extracts derived from roots of Scutellaria baicalensis and heartwoods of Acacia catechu containing free-B-ring flavonoids and flavans, respectively, were combined into a proprietary blend called UP326. A similar bioflavonoid composition, UP446, has been reported with modulation of pathways related to systemic inflammation. To test the effect of UP326 on memory and learning, a radial arm water maze (RAWM) and contextual fear conditioning (CF) were utilized in aged F344 rats fed with UP326 at doses of 3, 7, and 34 mg/kg for 11 weeks. The 7 and 34 mg/kg dosage groups had significantly fewer errors than aged vehicle control animals and their performance was equivalent to young animal controls. In a separate human clinical trial, test subjects orally given 300 mg of UP326 BID for 30 days showed marked improvement in speed and accuracy of processing complex information in computer tasks and reduced their standard deviation of performance compared to baseline and the placebo group. This data suggest that UP326 may help maintain memory, sustain speed of processing, and reduce the number or memory errors as we age.

In vivo safety evaluation of UP780, a standardized composition of aloe chromone aloesin formulated with an Aloe vera inner leaf fillet.

Safety profiles of the aloe chromone aloesin or Aloe vera inner leaf fillet (Qmatrix) as a well tolerated entity have been reported separately. UP780, a standardized composition of aloe chromone formulated with an Aloe vera inner leaf fillet, has shown a significant beneficial effect in lowering blood glucose and improving insulin resistance in human. Here we evaluate the safety of UP780 after a repeated 14 and 90-day oral administration in CD-1 mice. UP780 was given at doses of 100mg/kg/day, 500mg/kg/day and 1000mg/kg/day to groups of 10 male and 10 female for 90days or administered by oral gavage at a dose of 2g/kg/day to groups of 5 male and 5 female for 14days. Body weight, feed consumption, hematology, clinical chemistry and histopathologic evaluation were performed. UP780 at a dose of 1000mg/kg/day or at 2000mg/kg/day produced no treatment-related toxicity or mortality. Body weight gain or feed consumption was similar between groups. There was no test article-related microscopic change. Spontaneously occurring minor changes in clinical chemistry and hematology were observed. However, these changes were limited to one sex or were not dose correlated. UP780 was well tolerated in this strain. A dose of 2000mg/kg/day was identified as the NOAEL (no-observed-adverse-effect-level).

UP780, a chromone-enriched aloe composition improves insulin sensitivity.

BACKGROUND: Diabetic individuals experience elevated fasting glucose, glycosylated hemoglobin (HbA1c), and plasma insulin and impaired glucose tolerance. Adiponectin is a hormone inversely correlated with insulin resistance. Here we describe the activity of aloesin, an aloe chromone that increases adiponectin production and, when formulated with an aloe polysaccharide composition, improves the insulin sensitivity in db/db and diet-induced obese-diabetic mice. METHODS: Two aloe chromones, aloesin and aloesinol, were tested in vitro for adiponectin production. Following confirmation of glucose-lowering activity in a high-fat diet (HFD)-induced mouse model, aloesin was formulated with an Aloe vera inner leaf gel powder polysaccharide preparation to yield a composition designated UP780. Efficacy of UP780 was evaluated in HDF-induced and db/db mouse models. GW1929, a synthetic peroxisome proliferator-activated receptor-γ (PPARγ) agonist, was used as a positive control. RESULTS: After 3 weeks of treatment of HDF-induced mice, plasma insulin levels were decreased 37.9% and 46.7% by aloesin and aloesinol, respectively. In db/db mice, the chromone- (2% chromone:98% aloe polysaccharide) enriched UP780 aloe composition showed a 33.7% and 46.0% decrease in fasting triglyceride and plasma glucose levels after 10 weeks of oral treatment, respectively. Diabetic mice gavaged with 200 mg/kg of UP780 for 10 weeks showed a 30.3% decrease in fasting blood glucose levels and a 32.2% reduction in plasma insulin. In both animal models, UP780 showed a statistically significant improvement in blood glucose clearance. CONCLUSION: These findings indicate that UP780, a chromone-standardized, aloe-based composition, could potentially be used as a natural product option to facilitate the maintenance of healthy blood glucose levels.

Effects of Aloe vera supplementation in subjects with prediabetes/metabolic syndrome.

BACKGROUND: Metabolic syndrome affects 1 in 3 U.S. adults. The primary target of treatment of patients with metabolic syndrome is therapeutic lifestyle change. Numerous animal trials have reported positive effects of Aloe vera in in vivo models of diabetes, but there is a paucity of controlled clinical trials in patients with prediabetes. Thus, the objective of this pilot study was to examine the effect of aloe compared to placebo on fasting blood glucose, lipid profile, and oxidative stress in subjects with prediabetes/metabolic syndrome. METHODS: This was a double-blind, placebo-controlled Institutional Review Board (IRB)-approved pilot study of two aloe products (UP780 and AC952) in patients with prediabetes over an 8-week period. A total of 45 subjects with impaired fasting glucose or impaired glucose tolerance and having two other features of metabolic syndrome were recruited (n=15/group). Parameters of glycemia [fasting glucose, insulin, homeostasis model assessment (HOMA), glycosylated hemoglobin (HbA1c), fructosamine, and oral glucose tolerance test (OGTT)] and oxidative stress (urinary F2-isoprostanes) were measured along with lipid profile and high-sensitivity C-reactive protein (hsCRP) levels before and after supplementation. RESULTS: There were no significant baseline differences between groups. Compared to placebo, only the AC952 Aloe vera inner leaf gel powder resulted in significant reduction in total and low-density lipoprotein cholesterol (LDL-C) levels, glucose, and fructosamine. In the UP780 Aloe vera inner leaf gel powder standardized with 2% aloesin group, there were significant reductions in HbA1c, fructosamine, fasting glucose, insulin, and HOMA. Only the UP780 aloe group had a significant reduction in the F2-isoprostanes compared to placebo. CONCLUSIONS: Standardized aloe preparations offer an attractive adjunctive strategy to revert the impaired fasting glucose and impaired glucose tolerance observed in conditions of prediabetes/metabolic syndrome.

Analgesic effects of a standardized bioflavonoid composition from Scutellaria baicalensis and Acacia catechu.

Anti-inflammatory properties of both baicalin and catechins have been widely reported. However, the reports of analgesic effects of baicalin and catechins are limited. Three commonly used pain-related animal models were employed to evaluate the analgesic activity of UP446, a standardized bioflavonoid composition of baicalin and catechins. Carrageenan-induced paw edema, formalin test, and abdominal constriction assays were used to evaluate antinociceptive activity of 150 mg/kg or 100 mg/kg oral doses of UP446. Ibuprofen was used as a reference compound in each test. Pretreatment of carrageenan-induced hyperalgesic animals with UP446 at 150 mg/kg oral dosage reduced the hypersensitivity of pain by 39.5%. Similarly, a single dose of UP446, given orally at 100 mg/kg, exhibited 58% and 71.9% inhibition in pain sensitivity compared to vehicle-treated control in writhing and formalin tests, respectively. These findings suggest that the standardized anti-inflammatory bioflavonoid composition, UP446, could also be employed to inhibit nociception.

A randomized, double blind, placebo and active comparator controlled pilot study of UP446, a novel dual pathway inhibitor anti-inflammatory agent of botanical origin.

BACKGROUND: Current use of prescribed or over the counter non-steroidal anti-inflammatory drugs (NSAIDs) for pain and osteoarthritis (OA) have untoward gastrointestinal and cardiovascular related side effects, as a result the need for a safe and effective alternative has become unequivocally crucial. METHOD: A randomized, double blind, placebo and active controlled pilot study of a novel dual pathway, COX1/2 and LOX, inhibitor anti-inflammatory agent of botanical origin, UP446 was conducted. Sixty subjects (age 40-75) with symptomatic OA of the hip or knee were assigned to 4 treatment groups (n = 15); Group A0 (Placebo, CMC capsule), Group A1 (UP446 250 mg/day), Group A2 (UP446 500 mg/day) and Group A3 (Celecoxib, 200 mg/day). MOS-SF-36 and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) data were collected at baseline and after 30, 60 and 90 days of treatment as a measure of efficacy. Erythrocyte sedimentation rate, C-reactive protein, plasma thrombin time (PTT), fructosamine, Hematology, clinical chemistry and fecal occult blood were monitored for safety. RESULTS: Statistically significant decrease in WOMAC pain score were observed for Group A1 at day 90, Group A2 at 30 and 90 days and Group A3 at 60 and 90 days. Statistically significant decrease in WOMAC stiffness score were observed for Group A1 and Group A2 at 30, 60 and 90 days; but not for Group A0 and Group A3. The mean change in WOMAC functional impairment scores were statistically significant for Group A1 and Group A2 respectively at 30 days (p = 0.006 and p = 0.006), at 60 days (p = 0.016 and p = 0.002) and at 90 days (p = 0.018 and p = 0.002), these changes were not significant for Group A0 and Group A3. Based on MOS -SF-36 questionnaires, statistically significant improvements in physical function, endurance and mental health scores were observed for all active treatment groups compared to placebo. No significant changes suggestive of toxicity in routine hematologies, serum chemistries, liver enzymes or PTT were noted in any of the treatment groups. CONCLUSION: Based on current findings UP446 is safe and efficacious alternative to established anti-inflammatory medications for alleviating OA symptoms as measured by the WOMAC Index.

Screening a plant extract library for inhibitors of cholecystokinin receptor CCK1 pathways.

This study describes the screening of a plant extract library for inhibitors of signal transduction pathways mediated by the cholecystokinin receptor, CCK1. CCK1 receptors are coupled to Galpha(q/11)-proteins, localized mainly in the gastrointestinal tract, and implicated in the regulation of various digestive functions. A primary screen was performed using a cell-based assay that used the beta-lactamase gene reporter controlled by the transcriptional activator NFAT. The assay was validated with the CCK1 receptor antagonist, lorglumide, and automated by the use of a liquid-handling robot MultiProbe II. Off-target hits were triaged by counterscreening against gene reporter cells activated by a combination of thapsigargin and phorbol ester. Purification of active compounds was guided by the beta-lactamase gene reporter and Ca2+ mobilization assays. Pure compounds were characterized by Ca2+ mobilization, radioligand binding, inositol-1 phosphate formation, and Eu-GTP binding assays. The selectivity of inhibition was tested against a panel of Galpha(q/11), Galpha(s), and Galpha(i/0)-coupled receptors. These studies led to the identification of a novel Galpha(q/11)-selective inhibitor.