Curcumin is a polyphenol that is commonly used for its perceived health benefits. However, the absorption efficacy of curcumin is too low to exhibit beneficial effects. We have successfully developed ...a highly absorptive curcumin dispersed with colloidal nano-particles, and named it THERACURMIN. The absorption efficacy of THERACURMIN was investigated and compared with that of curcumin powder. The area under the blood concentration–time curve (AUC) after the oral administration of THERACURMIN was found to be more than 40-fold higher than that of curcumin powder in rats. Then, healthy human volunteers were administered orally 30 mg of THERACURMIN or curcumin powder. The AUC of THERACURMIN was 27-fold higher than that of curcumin powder. In addition, THERACURMIN exhibited an inhibitory action against alcohol intoxication after drinking in humans, as evidenced by the reduced acetaldehyde concentration of the blood. These findings demonstrate that THERACURMIN shows a much higher bioavailability than currently available preparations. Thus, THERACURMIN may be useful to exert clinical benefits in humans at a lower dosage.
Objectives: Fingertip injuries are common, and there are many techniques used for reconstruction. The authors reviewed the outcomes of fingertip reconstruction, including sensation and shape, using ...the combined technique of the adipofascial cross-finger flap and glabrous skin graft and defined the optimal dimensions of fingertip defect that is applicable to this technique. Methods: Between 2006 and 2016, 10 cases, aged 3-60 years (mean, 28.1 years), who had undergone fingertip reconstruction using a combination of the adipofascial cross-finger flap and glabrous skin graft were reviewed. The presence of fingertip and nail deformity and the results of the Semmes-Weinstein monofilament and static two-point discrimination tests were analyzed. Results: Fingertip deformity was noted in three cases where the defect was more than 50% of the Tamai zone I or extended to zone II. Mild nail plate deformity was found in three cases with more than 40% of the nail bed defect. Two of these three cases presented with partial phalangeal tuft defects. Eight fingers were examined using the Semmes-Weinstein test, and their scores were between 2.83 and 4.31 in five fingers and 4.56 in three fingers. Six were examined for static two-point discrimination, with 5 mm in three, 6 mm in one, and 10 mm in two. The color and contour of all donor fingers were almost typical. Conclusions: The combination of the adipofascial cross-finger flap and full-thickness glabrous skin graft is applicable to around 50% of fingertip defect within the Tamai zone I, achieving a satisfactory shape and regaining more than protective sensation.
Background We previously developed a surface-controlled water-dispersible form of curcumin and named it Theracurmin® (Theracurmin; Theravalues, Tokyo, Japan). The area under the blood ...concentration–time curve of Theracurmin in humans was 27-fold higher than that of curcumin powder. We determined the clinical effects of orally administered Theracurmin in patients with knee osteoarthritis during 8 weeks of treatment.
Methods Fifty patients with knee osteoarthritis of Kellgren–Lawrence grade II or III and who were aged more than 40 years were enrolled in this randomized, double-blind, placebo-controlled, prospective clinical study. Placebo or Theracurmin containing 180 mg/day of curcumin was administered orally every day for 8 weeks. To monitor adverse events, blood biochemistry analyses were performed before and after 8 weeks of each intervention. The patients’ knee symptoms were evaluated at 0, 2, 4, 6, and 8 weeks by the Japanese Knee Osteoarthritis Measure, the knee pain visual analog scale (VAS), the knee scoring system of the Japanese Orthopedic Association, and the need for nonsteroidal anti-inflammatory drugs.
Results At 8 weeks after treatment initiation, knee pain VAS scores were significantly lower in the Theracurmin group than in the placebo group, except in the patients with initial VAS scores of 0.15 or less. Theracurmin lowered the celecoxib dependence significantly more than placebo. No major side effects were observed with Theracurmin treatment.
Conclusion Theracurmin shows modest potential for the treatment of human knee osteoarthritis.
Obliteration of an organized subphrenic abscess with an enteric fistula is a great challenge, especially after hepatectomy, as most of the conventional flaps used to fill the abscess cavity are not ...feasible. A seromuscular flap is an innovative option for this purpose because of its proximity to the pathology, flexibility in the size and volume of the flap harvested, antibacterial ability of the muscle flap, and preservation of trunk musculature. We illustrate the use of a colonic seromuscular flap for filling such an abscess and show its long-term change. A 66-year-old man developed a right subphrenic abscess after subsegmentectomy for his hepatocellular carcinoma. Prolonged percutaneous drainage of the abscess was unsuccessful because of the enteric communication with the transverse colon and resulted only in the organization of the abscess cavity. Through the previous laparotomy incision, the involved part of the transverse colon was detached from the abscess. The transverse colon including the fistula was isolated for 16 cm based on the middle colic vessels. Following an enterotomy along the antimesenteric border and mucosal stripping, a colonic seromuscular flap was made. The debrided abscess cavity was properly filled with this flap. The donor colon was repaired. The postoperative course was uneventful without showing any signs of infection for more than 3 years. During this period, the volume of the flap filling the cavity showed significant reduction of 50%. The seromuscular colonic flap is an effective option for filling the intra-abdominal abscess cavity when most of the conventional flaps are not feasible.
Scope
Glucagon‐like peptide‐1 (GLP‐1) is a type of incretin secreted from enteroendocrine L‐cells. Our previous studies demonstrated that curcumin (a yellow pigment of turmeric) significantly ...increases the secretion of GLP‐1 in enteroendocrine L cell line (GLUTag cells). However, it is not clear whether its action in vivo directly enhances GLP‐1 secretion, which then leads to a reduction in blood glucose levels via the stimulation of insulin secretion. In addition, the molecular target of curcumin‐induced GLP‐1 secretion has not been clarified.
Methods and results
Glucose tolerance was significantly improved in rats after pre‐administered curcumin (1.5 mg/kg) followed by intraperitoneal glucose injections via the stimulation of GLP‐1 secretion and the induction of insulin secretion. In GLUTag cells, curcumin‐induced GLP‐1 secretion was associated with G protein‐coupled receptor (GPR) 40/120. Furthermore, the glucose‐lowering effect induced by curcumin was significantly reduced after the administration of a GPR40/120 antagonist in rats.
Conclusion
These findings demonstrate the biological function of curcumin as a GLP‐1 secretagogue and the possible molecular target that mediates GLP‐1 secretion. Increases in the secretion of endogenous GLP‐1 induced by curcumin may allow the dosages of other diabetic medicines to be reduced and aid in the prevention of diabetes.
GLP‐1 stimulates glucose‐dependent insulin secretion, and is an important factor in the treatment and prevention of type 2 diabetes. It is demonstrated that oral administration of curcumin significantly increases the plasma concentrations of GLP‐1 and insulin, resulting in the amelioration of impaired glucose tolerance in rats, and also curcumin‐induced GLP‐1 secretion is mediated via GPR 40/120 pathway.
Curcumin, a polyphenol derived from the rhizome of the naturally occurring plant Curcuma longa, has various pharmacological actions such as antioxidant and anti-inflammatory effects. In this paper, ...we evaluated the role of its internal metabolite, curcumin β-D-glucuronide (curcumin monoglucuronide, CMG), by investigating curcumin kinetics and metabolism in the blood. Firstly, we orally administered highly bioavailable curcumin to rats to elucidate its kinetics, and observed not only the free-form of curcumin, but also, curcumin in a conjugated form, within the portal vein. We confirmed that curcumin is conjugated when it passes through the intestinal wall. CMG, one of the metabolites, was then orally administered to rats. Despite its high aqueous solubility compared to free-form curcumin, it was not well absorbed. In addition, CMG was injected intravenously into rats in order to assess its metabolic behavior in the blood. Interestingly, high levels of free-form curcumin, thought to be sufficiently high to be pharmacologically active, were observed. The in vivo antitumor effects of CMG following intravenous injection were then evaluated in tumor-bearing mice with the HCT116 human colon cancer cell line. The tumor volume within the CMG group was significantly less than that of the control group. Moreover, there was no significant loss of body weight in the CMG group compared to the control group. These results suggest that CMG could be used as an anticancer agent without the serious side effects that most anticancer agents have.
•Development of highly bioavailable curcumin (Theracurmin).•Effect of curcumin on cancer.•Effect of curcumin on cardiovascular disease.•Effect of curcumin supplementation and aerobic exercise ...training on arterial compliance.•Effect of curcumin supplementation on exercise-induced oxidative stress, inflammation, and muscle damage.
Curcumin is a polyphenol with antioxidant and anti-inflammatory properties. It is highly lipophilic and sparingly soluble in water and very little is absorbed when it is ingested; therefore, improving its absorbability is a major priority. We developed a highly bioavailable curcumin called Theracurmin using submicron particle formation and surface controlled technology. In human study, the area under the blood concentration–time curve (AUC) after oral administration of Theracurmin was 27-fold higher than that of commercially available curcumin. Preclinical safety tests were conducted and no adverse effects were confirmed. The effects of Theracurmin on cancer (lung, pancreatic, and prostate), cardiovascular disease (heart disease), vascular function (arterial stiffness and central blood pressure), and bone and cartilage (knee osteoarthritis) were evaluated by collaborating with universities and medical institutions. In this paper, we present the development of Theracurmin and its effects in an animal model as well as in human clinical studies.
Background
A growing number of preclinical studies have demonstrated that curcumin could be a promising anticancer drug; however, poor bioavailability has been the major obstacle for its clinical ...application. To overcome this problem, we developed a new form of curcumin (Theracurmin
®
) and reported high plasma curcumin levels could be safely achieved after a single administration of Theracurmin
®
in healthy volunteers. In this study, we aimed to evaluate the safety of repetitive administration of Theracurmin
®
in cancer patients.
Methods
Pancreatic or biliary tract cancer patients who failed standard chemotherapy were eligible for this study. Based on our previous pharmacokinetic study, we selected Theracurmin
®
containing 200 mg of curcumin (Level 1) as a starting dose, and the dose was safely escalated to Level 2, which contained 400 mg of curcumin. Theracurmin
®
was orally administered every day with standard gemcitabine-based chemotherapy. In addition to safety and pharmacokinetics data, NF-κB activity, cytokine levels, efficacy, and quality-of-life score were evaluated.
Results
Ten patients were assigned to level 1 and six were to level 2. Peak plasma curcumin levels (median) after Theracurmin
®
administration were 324 ng/mL (range, 47–1,029 ng/mL) at Level 1 and 440 ng/mL (range, 179–1,380 ng/mL) at Level 2. No unexpected adverse events were observed and 3 patients safely continued Theracurmin
®
administration for >9 months.
Conclusions
Repetitive systemic exposure to high concentrations of curcumin achieved by Theracurmin
®
did not increase the incidence of adverse events in cancer patients receiving gemcitabine-based chemotherapy.
Purpose
Polyphenolic curcumin is known to have potent anti-inflammatory effects; thus the present study investigated the hypothesis that curcumin ingestion would attenuate muscle damage after ...eccentric exercise.
Methods
Fourteen untrained young men (24 ± 1 years) performed 50 maximal isokinetic (120°/s) eccentric contractions of the elbow flexors of one arm on an isokinetic dynamometer and the same exercise with the other arm 4 weeks later. They took 150 mg of curcumin (theracurmin) or placebo (starch) orally before and 12 h after each eccentric exercise bout in a randomised, crossover design. Maximal voluntary contraction (MVC) torque of the elbow flexors, range of motion of the elbow joint, upper-arm circumference, muscle soreness, serum creatine kinase (CK) activity, and plasma interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentration were measured before, immediately after, and 24, 48, 72 and 96 h after each eccentric exercise. Changes in these variables over time were compared between curcumin and placebo conditions by two-way repeated measures ANOVA.
Results
MVC torque decreased smaller and recovered faster (e.g., 4 days post-exercise: −31 ± 13 % vs. −15 ± 15 %), and peak serum CK activity was smaller (peak: 7684 ± 8959 IU/L vs. 3398 ± 3562 IU/L) for curcumin than placebo condition (
P
< 0.05). However, no significant differences between conditions were evident for other variables, and no significant changes in IL-6 and TNF-α were evident after exercise.
Conclusion
It is concluded that theracurmin ingestion attenuates some aspects of muscle damage such as MVC loss and CK activity increase.
We sought to determine the preventive effects of curcumin and its highly bioavailable preparation on noise-induced hearing loss in a novel murine model of permanent hearing loss developed by repeated ...exposure to noise. Upon exposure to noise (8-kHz octave band noise, 90 dB sound pressure level, 1 h), hearing ability was impaired in a temporary and reversible manner. During repeated noise exposure (1-h exposure per day, 5 days), there was a progressive increase in the auditory threshold shift at 12 and 20 kHz. The threshold shift persisted for at least 6 days after noise exposure. Oral administration of curcumin for 3 days before and each day during noise exposure significantly alleviated the hearing loss induced by repeated noise exposure. Curcumin abolished intranuclear translocation of nuclear factor-κB-p65 and generation of 4-hydroxynonenal-adducted proteins found in the cochlea after noise exposure. Theracurmin®, a highly absorbable and bioavailable preparation of curcumin, had strong preventive effects on hearing loss induced by repeated noise exposure. Together, these data suggest that curcumin exerts a preventive effect on noise-induced hearing loss and is therefore a good therapeutic candidate for preventing sensorineural hearing loss.
PDF
