A Standardized Botanical Composition Mitigated Acute Inflammatory Lung Injury and Reduced Mortality through Extracellular HMGB1 Reduction.

HMGB1 is a key late inflammatory mediator upregulated during air-pollution-induced oxidative stress. Extracellular HMGB1 accumulation in the airways and lungs plays a significant role in the pathogenesis of inflammatory lung injury. Decreasing extracellular HMBG1 levels may restore innate immune cell functions to protect the lungs from harmful injuries. Current therapies for air-pollution-induced respiratory problems are inadequate. Dietary antioxidants from natural sources could serve as a frontline defense against air-pollution-induced oxidative stress and lung damage. Here, a standardized botanical antioxidant composition from Scutellaria baicalensis and Acacia catechu was evaluated for its efficacy in attenuating acute inflammatory lung injury and sepsis. Murine models of disorders, including hyperoxia-exposed, bacterial-challenged acute lung injury, LPS-induced sepsis, and LPS-induced acute inflammatory lung injury models were utilized. The effect of the botanical composition on phagocytic activity and HMGB1 release was assessed using hyperoxia-stressed cultured macrophages. Analyses, such as hematoxylin-eosin (HE) staining for lung tissue damage evaluation, ELISA for inflammatory cytokines and chemokines, Western blot analysis for proteins, including extracellular HMGB1, and bacterial counts in the lungs and airways, were performed. Statistically significant decreases in mortality (50%), proinflammatory cytokines (TNF-α, IL-1ß, IL-6) and chemokines (CINC-3) in serum and bronchoalveolar lavage fluid (BALF), and increased bacterial clearance from airways and lungs; reduced airway total protein, and decreased extracellular HMGB1 were observed in in vivo studies. A statistically significant 75.9% reduction in the level of extracellular HMGB1 and an increase in phagocytosis were observed in cultured macrophages. The compilations of data in this report strongly suggest that the botanical composition could be indicated for oxidative-stress-induced lung damage protection, possibly through attenuation of increased extracellular HMGB1 accumulation.

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.

A Clinical Study Evaluating the Efficacy of Topical Bakuchiol (UP256) Cream on Facial Acne.

Acne vulgaris is a common skin disease that manifests clinically as comedones, papules, nodules, and cysts. In this single center, open-label pilot study (ISRCTN13992386), we aimed to evaluate the effectiveness of UP256 cream, a newly patented topical product containing 0.5% bakuchiol, on facial acne and acne-related post-inflammatory hyperpigmentation (PIH). A series of 13 subjects enriched for Fitzpatrick skin types III–VI with mild or moderate acne received treatment with UP256 twice daily for 12 weeks. Efficacy assessments included changes in inflammatory and non-inflammatory lesions as well as a reduction in Evaluator Global Severity Score (EGSS) assessments of acne severity and PIH. Safety, adverse events, and cutaneous tolerability were evaluated throughout the study. UP256 significantly reduced the number of inflammatory lesions and improved existing PIH. UP256 was also cosmetically acceptable and well tolerated by all study subjects. Overall, our results demonstrate that monotherapy with UP256 improves mild to moderate acne and may be particularly well suited for individuals with skin of color. J Drugs Dermatol. 2021;20(3):307-310. doi:10.36849/JDD.5655.

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.

Protective Effect of UP446 on Ligature-Induced Periodontitis in Beagle Dogs.

Periodontal disease is an inflammatory disease of the gum caused by a formation of a plaque that triggers immune responses and inflammation leading to the destruction of tissues surrounding and supporting the teeth. Chronic usage of synthetic chemicals and antibiotics is limited by undesired adverse events to the host. A botanical composition (UP446), which consists primarily of bioflavonoids such as baicalin from roots of Scutellaria baicalensis and catechins from heartwoods of Acacia catechu, was evaluated for its effect on ligature-induced periodontal disease in beagle dogs. Disease model was induced in 20 male and female dogs. After a 12-week induction of periodontitis, animals were assigned to a placebo, positive control (doxycycline), and two treatment groups consisting of five animals each. The placebo group was only administrated to normal dog chow (25 g/kg/day). In the doxycycline treatment group, animals were fed a normal diet (25 g/kg/day) and doxycycline (5 mg/kg) was orally administrated every day. Treatment of UP446 was done by feeding the regular diet formulated with 0.1% and 0.2% of UP446 by weight. Clinical indices such as plaque index (PI), gingival index (GI), clinical attachment level (CAL), probing pocket depth (PPD), and bleeding on probing (BoP) were measured every two weeks for 12 weeks. UP446 administered to beagle dogs for 12 weeks at 0.1% and 0.2% resulted in statistically significant reductions in gingivitis, pocket depth, loss of attachment, and gum bleeding. UP446 could potentially be used alone or as an adjunct with other oral hygiene preparations for periodontal disease in both human and companion animals.

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.

A Randomized, Active Comparator-controlled Clinical Trial of a Topical Botanical Cream for Skin Hydration, Elasticity, Firmness, and Cellulite.

Background: The skin is where initial visual signs of aging manifest, including increased skin dryness and decreased firmness and elasticity. Cellulite, a skin condition characterized by changes in the skin morphology due to excessive lipid deposition in subcutaneous adipose tissue, is another characteristic of skin aging. Objective: We sought to assess the effectiveness of a topical botanical cream on cellulite, skin hydration, firmness, and elasticity after two, four, and eight weeks of use compared to an active comparator. Design: The study was a single-blind, randomized, controlled study conducted on subjects with mild-to-severe cellulite on the thighs. Subjects were treated with a topical botanical cream (UP1307) and an active comparator for eight weeks. A total of 44 women 18 to 59 years of age were enrolled. Test products were gently applied in a circular motion to the area identified by subjects as the target cellulite area twice per day. Measurements: Measurements using Corneometer® (for skin hydration) and Cutometer® (for skin elasticity and firmness) were carried out at each visit in addition to expert clinical grader evaluations for cutaneous changes and cellulite. Outcomes were also assessed by patients using subject questionnaires. Results: Patients reported significant improvement in skin hydration, firmness, and elasticity over time. Findings were corroborated with objective instrumental measurements. At Week 8, 44.4- and 42.7-percent improvement in appearance of cellulite was also observed for the UP1307 cream and the active comparator group, respectively. Conclusion: Use of UP1307 cream produced significant improvements in skin hydration, firmness, and elasticity, with associated improvement in cellulite appearance. There was overall superiority of UP1307 between groups. Progressive subject perceptions of product effects are reported.

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.

AmLexin, a Standardized blend of Acacia catechu and Morus alba, shows benefits to delayed onset muscle soreness in healthy runners.

PURPOSE: Sudden and exhaustive exercise causes muscle damage accompanied by oxidative stress and inflammation, leading to muscle fatigue and soreness. AmLexin contains a standardized blend of extracts from the heartwood of Acacia catechu and the root bark of Morus alba, and is known to possess antioxidant and anti-inflammatory properties. The aim of this study was to investigate the effects of this proprietary blend supplementation on muscular pain and redox balance in healthy runners, in comparison to a placebo. METHODS: A double-blind placebo-controlled clinical trial was carried out over 9 weeks in a single center. Thirty physically active male and female subjects within 18-70 years of age were randomized into AmLexin (mean age = 42.92 ± 2.48 and gender 7/5, male/female, respectively) and placebo (mean age = 41.15 ± 3.5 and gender 10/3, male/female, respectively) groups. Subjects were supplemented with 400 mg of AmLexin/day or a look-alike placebo during an 8-week training program, and for one week following a 13.1-mile half-marathon. Twenty-six subjects completed the 9-week supplementation trial. RESULTS: Results showed the AmLexin group experienced significantly lower levels of post-exercise pain on day 1-3 following the half-marathon compared to the placebo group. The AmLexin group also showed lower post-exercise oxidative stress and higher antioxidant capacity on days 1 and 6 following the half-marathon. These results demonstrated the rapid benefits of AmLexin on pain and oxidative stress within 1-6 days post-exercise. CONCLUSION: Our data suggest that AmLexin could be a safe, effective botanical alternative for delayed onset muscle soreness.

A Standardized Composition Comprised of Extracts from Rosmarinus officinalis, Annona squamosa and Zanthoxylum clava-herculis for Cellulite.

BACKGROUND: Cellulite, characterized by changes in the skin morphology presented as dimpled or puckered skin appearance, is highly prevalent among postadolescent women. Cellulite management ranges from topical cream applications to invasive procedures. While some interventions showed improvements in physical appearances of affected areas, so far, none have reversed the condition to a full recovery. These unsuccessful measures signify the intricate nature of cellulite etiology highlighting its complexity leading to the possibility for a combination treatment approach to target multiple mechanisms. MATERIALS AND METHODS: We screened our plant library for extracts that reduce cellular lipid accumulation, improve microcirculation, possess high total antioxidant capacity, significant anti-platelet aggregation, and anti-inflammatory activities using lipid accumulation assay in 3T3-L1 cells, Croton oil-induced hemorrhoid test in rats as a model for microcirculation, anti-platelet aggregation assay, nitric oxide (NO) inhibition assay, and 1,1-diphenyl-2-picrylhydrazyl assay. RESULTS: Three known botanicals such as Rosemary officinalis, Annona squamosa and Zanthoxylum clava-herculis were identified as lead extracts in these tests. Treatment of 3T3 cell with A. squamosa at 1 µg/ml resulted in 68.8% reduction in lipid accumulation. In croton oil-induced hemorrhoid study, Z. clava-herculis reduced the recto-anus coefficient by 79.6% at 6 mg/kg indicating improvement in microcirculations. Similarly, R. officinalis caused inhibition of 82%, 71.8%, and 91.8% in platelet aggregation, NO production and free radical generation at 31.25 µg/ml, 6.2 µg/ml, and 40 µg/ml concentrations suggesting its anti-oxidant, and anti-inflammatory activities. CONCLUSIONS: Data depicted here suggest that formulation of these well-known botanicals at a specific ratio perhaps may yield a composition with a much wider spectrum of mechanisms of actions to impact the multiple pathways involved in cellulite onset, continuation, or exacerbations. SUMMARY: Cellulite represents one of the main esthetic concerns of women with a likely cause of psychological insecurities. Its pathophysiology involves multiple pathways that include vascular, adipose tissues, inflammation, structural and physiological.Treatment strategies for cellulite comprises increasing microcirculation flow, reducing lipogenesis, promoting lipolysis, free radicals scavenging or formation reduction, anti-inflammation and other invasive procedures.We screened our plant library for extracts that reduces cellular lipid accumulation, improves microcirculation, possesses high total antioxidant capacity, inhibits platelet aggregation, and moderates inflammation.Botanical extracts from Rosmarinus officinalis, Annona squamosa and Zanthoxylum clava-herculis were identified as leads and formulated to yield a standardized composition designated as UP1307 and suggested its usage for cellulite. Abbreviations Used: GMP: Good Manufacturing Practice; CA: Carnosic acid; NF-kB: nuclear factor-kB; HPLC: high-performance liquid chromatography; EtOH: Ethanol; DMEM: Dulbecco's modified Eagle's medium; FBS: fetal bovine serum; SD: Sprague Dawley; RAC: recto-anus coefficient; LPS: Lipopolysaccharide; DPPH: 1,1-diphenyl-2-picryl-hydrazyl; TNF-α: tumor necrosis factor; NO: Nitric oxide.

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.

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 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.

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.

UP1306, a Botanical Composition with Analgesic and Anti-inflammatory Effect.

BACKGROUND: Pain, one of the cardinal signs of inflammation, is the most common clinical manifestations of arthritis. Conventional pain relief therapy heavily relies on the use of prescription and over the counter nonsteroidal anti-inflammatory drugs as the first line of defense where their long-term usage causes deleterious gastrointestinal and cardiovascular-related side-effects. Hence, there is an equivocal need for evidence-based safer and efficacious alternatives from natural sources to overcome the most prominent and disabling symptoms of arthritis. MATERIALS AND METHODS: Carrageenan-induced rat paw edema and abdominal constriction (writhing's) assays in mouse were used to evaluate the anti-inflammatory and analgesic effects of UP1306, a composition that contains a standardized blend of extracts from the heartwood of Acacia catechu and the root bark of Morus alba administered orally at dose ranges of 100-300 mg/kg. Cyclooxygenase (COX) and lipoxygenase (LOX) inhibition assays were carried out to determine the IC50 of Acacia and Morus extracts. The merit of combining these two extracts was also assessed. RESULTS: Statistically significant improvement in pain resistance and suppression of edema were observed in animals treated with UP1306, when compared to vehicle-treated diseased rats and mice. Results from the high dose of UP1306 (300 mg/kg) were similar to those achieved by ibuprofen treatment at a dose of 200 mg/kg in early hours of treatment. In vitro, UP1306 showed dose-dependent inhibition of the enzymatic activities of COX and LO with IC50 values of 20.9 µg/mL, 49.2 µg/mL, and 11.1 µg/mL in COX-1, COX-2, and 5'-LO, respectively. CONCLUSIONS: These data suggest that UP1306, analgesic, and anti-inflammatory agent of botanical origin with dual COX-LO inhibition activity, could potentially be used to alleviate symptom associated to osteoarthritis. SUMMARY: Pain is the most common clinical manifestations of arthritisCarrageenan-induced rat paw edema and abdominal constriction (writhing's) assays in mouse are among the widely used models to evaluate the anti-inflammatory and analgesic effects of nutraceuticalsCyclooxygenase and lipoxygenase (LO) inhibition assays were carried out to determine the IC50 of Acacia and Morus extracts.Efficacy of UP1306, a composition containing a blend of two standardized extracts from the heartwood of Acacia catechu and root bark of Morus alba, was evaluated in the above models.UP1306 demonstrated its enhanced significance by improving the major cardinal signs of arthritis in vivo and inflammation markers in vitro.UP1306 could potentially be considered as a dietary supplement product for the management of arthritis.

UP1304, a Botanical Composition Containing Two Standardized Extracts of Curcuma longa and Morus alba, Mitigates Pain and Inflammation in Adjuvant-induced Arthritic Rats.

BACKGROUND: Though, the initial etiologies of arthritis are multifactorial, clinically, patients share pain as the prime complaints. Present day pain relief therapeutics heavily relies on the use of prescription and over the counter nonsteroidal anti-inflammatory drugs as the first line of defense where their long-term usage causes gastrointestinal and cardiovascular-related side effects. Hence, the need for evidence-based safer and efficacious alternatives from natural sources to overcome the most prominent and disabling symptoms of arthritis is an overdue. Here, we evaluated the anti-inflammatory and analgesic effect of UP1304, a composition that contains a standardized blend of two extracts from the rhizome of Curcuma longa and the root bark of Morus alba in adjuvant-induced arthritis models in rats. MATERIALS AND METHODS: The anti-inflammatory and analgesic effects of the botanical composition were demonstrated in adjuvant-induced arthritis models in rats with oral dose ranges of 50-200 mg/kg. Ibuprofen at a dose of 100 mg/kg was used as a reference compound. Ex vivo sulfated glycosaminoglycan inhibition assays were performed. RESULTS: Statistically significant improvements in pain resistance, suppression of paw edema and ankle thickness were observed in animals treated with UP1304 compared to vehicle-treated diseased rats. These results were similar to those achieved by ibuprofen treatment. Inhibitions of proteoglycan degradation were observed in a range of 37.5-61.7% for concentration of UP1304 at 50-200 µg/mL when compared to interleukin-1α-exposed untreated explants. CONCLUSIONS: These data suggest that UP1304, for its analgesic and anti-inflammatory effects, could potentially be considered agent of botanical origin for the improvement of arthritis associated symptoms. SUMMARY: Pain is one of the cardinal signs of arthritis.Long term applications of commonly used non-steroidal anti-inflammatory drugs for pain relief are associated with cardiovascular and gastrointestinal side effects.Cartilage degradation evidenced as glycosaminoglycan loss from articular cartilage into the synovial fluid has been reported in arthritis patients.Adjuvant-induced arthritis model in rats are among the widely used models for efficacy evaluation of nutraceuticals.Efficacy of UP1304, a composition containing a blend of two standardized extracts from the rhizome of Curcuma longa and root bark of Morus alba, was evaluated in adjuvant-induced arthritis model in rats and in glycosaminoglycan releasing inhibition assays.UP1304 demonstrated its enhanced significance by improving the major cardinal signs of arthritis in vivo and ex vivo.UP1304 could potentially be considered as a dietary supplement product for the management of arthritis.