Isoflavone intervention and its impact on bone mineral density in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials.

Due to estrogen deficiency, postmenopausal women may suffer from an imbalance in bone metabolism that leads to bone fractures. Isoflavones, a type of phytoestrogen, have been suggested to improve bone metabolism and increase bone mass. Therefore, isoflavones are increasingly recognized as a promising natural alternative to hormone replacement therapy for postmenopausal women who face a heightened risk of osteoporosis and are susceptible to bone fractures. PURPOSE: This study aimed to evaluate the efficacy of isoflavone interventions on bone mineral density (BMD) in postmenopausal women by means of systematic review and meta-analysis. METHODS: The electronic database searches were performed on PubMed, Embase, Scopus, and Cochrane Library databases, covering literature up to April 20, 2023. A random-effects model was used to obtain the main effect estimates, with a mean difference (MD) and its 95% confidence interval (CI) as the effect size summary. The risk of bias assessment was conducted using the Risk of Bias 2 (RoB2) tool. RESULTS: A total of 63 randomized controlled trials comparing isoflavone interventions (n = 4,754) and placebo (n = 4,272) were included. The results indicated that isoflavone interventions significantly improved BMD at the lumbar spine (MD = 0.0175 g/cm2; 95% CI, 0.0088 to 0.0263, P < 0.0001), femoral neck (MD = 0.0172 g/cm2; 95% CI, 0.0046 to 0.0298, P = 0.0073), and distal radius (MD = 0.0138 g/cm2; 95% CI, 0.0077 to 0.0198, P < 0.0001) in postmenopausal women. Subgroup analysis showed that the isoflavone intervention was effective for improving BMD when the duration was ≥ 12 months and when the intervention contained genistein of at least 50 mg/day. CONCLUSION: This systematic review and meta-analysis suggests that isoflavone interventions, especially those containing genistein of at least 50 mg/day, can effectively enhance BMD in postmenopausal women.

Efficacy and Safety of the Genistein Nutraceutical Product Containing Vitamin E, Vitamin B3, and Ceramide on Skin Health in Postmenopausal Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Skin aging is one of the most concerning issues that occur after menopause. The Genistein Nutraceutical (GEN) product, containing genistein, vitamin E, vitamin B3, and ceramide, has been formulated as a topical anti-aging product for improving the health of postmenopausal women's facial skin. This study aimed to investigate the efficacy and safety of the GEN product on postmenopausal women's facial skin. This randomized, double-blind, placebo-controlled trial randomly assigned 50 postmenopausal women to receive either the GEN product (n = 25) or the placebo (PLA) product (n = 25), topically applied twice daily for 6 weeks. The outcome assessments included multiple skin parameters related to skin wrinkling, color, hydration, and facial skin quality at baseline and week 6. The percentage mean changes or absolute mean changes, where appropriate, in skin parameters were compared between the two groups. The mean age of the participants was 55.8 ± 3.4 years. For skin wrinkling and skin color parameters, only skin redness was significantly higher in the GEN group when compared to the PLA group. Following the application of the GEN product, skin hydration increased while fine pores and their area decreased. Subgroup analysis of older women (age ≥ 56 years) with adequate compliance found significant differences between the two groups in the percentage mean changes of most skin wrinkle parameters. The GEN product has benefits for the facial skin of postmenopausal women, particularly those who are older. It can moisturize facial skin, lessen wrinkles, and enhance redness.

A Randomized Controlled Trial of Thai Medicinal Plant-4 Cream versus Diclofenac Gel in the Management of Symptomatic Osteoarthritis of the Knee.

Background: Osteoarthritis of the knee is a common degenerative musculoskeletal condition. Thai Medicinal Plant-4 (TMP-4) cream is made up of Garcinia mangostana peel, Sesamum indicum seeds, Glycine max (L.) Merr. seeds, and Centella asiatica leaves, all of which have anti-inflammatory and analgesic properties. The present study aimed at determining the efficacy and safety of TMP-4 cream versus diclofenac gel in the treatment of symptomatic osteoarthritis of the knee. Methods: A randomized-controlled trial was conducted to assess knee pain on a scale of 100 mm Visual Analog Scale (VAS) and other key metrics, including VAS knee stiffness, a modified 10-step stair climb test, a timed up and go test, the Knee Injury and Osteoarthritis Outcome Score, and safety outcomes, following administration of either TMP-4 cream or diclofenac gel for 4 weeks. Results: A total of 199 patients with moderate knee pain intensity were randomly assigned to either TMP-4 cream or diclofenac gel (allocation ratio 1 : 1). The mean changes of VAS knee pain in the TMP-4 cream and diclofenac gel groups were -31.68 ± 14.18 mm and -31.09 ± 12.41 mm, respectively, (mean difference = -0.58, 95% confidence interval = -4.37-3.20, P=0.761). The upper limit of 95% confidence interval for the comparison between TMP-4 cream and diclofenac gel was within the predefined margin of 7 mm for noninferiority. The safety was comparable between the two interventions. Conclusions: TMP-4 cream was noninferior to diclofenac gel in relieving osteoarthritic knee pain and may be considered as an alternative therapeutic option in the treatment of symptomatic osteoarthritis of the knee.

Mycophenolic acid and cancer risk in solid organ transplant recipients: Systematic review and meta-analysis.

AIM: Mycophenolic acid (MPA) is an immunosuppressive drug commonly used for prophylaxis of graft rejection in solid organ transplant recipients. The main concern with the prolonged use of immunosuppressive drugs is the risk of developing cancer. However, it remains unclear whether the immunosuppressive regimens containing MPA confer an increased degree of cancer risk. The present study aimed to determine the association between MPA exposure and the incidence of cancer in solid organ transplant recipients. METHODS: A systematic search was performed on the PubMed, EMBASE and Cochrane Library databases. Relevant articles that had findings on the incidence (or event) of cancer in cohorts with and without MPA exposure were retrieved for data extraction. A meta-analysis was conducted by means of the random-effects model, and the relative risk (RR) and its 95% confidence interval (95% CI) were used as a summary effect measure. RESULTS: A total of 39 studies were eligible for inclusion, with 32 studies that enabled meta-analysis. MPA exposure was significantly associated with a lower risk of cancer when compared to azathioprine exposure (RR = 0.66, 95% CI = 0.53-0.81, P < .001) or no exposure to any additional treatments (RR = 0.85, 95% CI = 0.73-0.99, P = .04). There was no significant difference in cancer risk for the comparison between MPA exposure and mammalian target of rapamycin (mTOR) inhibitor exposure (RR = 1.54, 95% CI = 0.96-2.46, P = .07). CONCLUSIONS: MPA exposure was not associated with an increased risk of cancer and may even be associated with a lower risk of cancer when compared to azathioprine or no treatment.

Clinical Efficacy and Safety of Thai Herbal Formulation-6 in the Treatment of Symptomatic Osteoarthritis of the Knee: A Randomized-Controlled Trial.

BACKGROUND: Osteoarthritis of the knee is the most common form of arthritis. Identifying effective and safe herbal formulations that are locally available is viewed as a priority for sustainable development in a region. This study aimed to evaluate the efficacy and safety of Thai herbal formulation-6 (THF-6) in comparison with oral diclofenac in patients with moderate-to-severe osteoarthritis of the knee. METHODS: This randomized, double-blind, active-controlled, noninferiority trial randomly assigned patients with osteoarthritis of the knee to receive either THF-6 or diclofenac for four weeks. The primary outcome measure was the change from baseline in knee pain as measured by a 100 mm visual analog scale (VAS). Secondary outcome measures included knee stiffness, a stair climb test, the Knee Injury and Osteoarthritis Outcome Score, and safety parameters. Outcomes were assessed on a biweekly basis. Modified intention-to-treat (MITT) and perprotocol (PP) analyses were applied. RESULTS: A total of 200 patients were enrolled of whom 175 (87.5%) were included in the MITT analysis and 153 (76.5%) in the PP analysis. The mean change in VAS pain did not differ between the two groups, and the upper limit of the two-sided 95% confidence interval (CI) for comparison between the two groups was within the prespecified margin of 10 mm for noninferiority (MITT analysis: mean difference = 0.86, 95% CI = -4.39 to 6.10, p=0.748; PP analysis: mean difference = 1.98, 95% CI = -3.61 to 7.56, p=0.486). Significant improvement was observed in all the efficacy parameters in both groups. Dyspepsia was the most common adverse event: 23 patients in the THF-6 group and 28 in the diclofenac group (p=0.417). CONCLUSIONS: THF-6 offers an alternative to oral diclofenac for the short-term treatment of osteoarthritis of the knee. It was shown to be noninferior to oral diclofenac in relieving knee pain. This trial is registered with ChiCTR-IPR-15007213.

Adverse pregnancy outcomes associated with first-trimester exposure to angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers: A systematic review and meta-analysis.

This study aimed to determine the effects of prenatal exposure to angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), particularly when exposure is limited to the first trimester of pregnancy, on adverse maternal and neonatal outcomes. A systematic search was performed on four databases, that is, PubMed, Scopus, Web of Science, and Cochrane Library, to identify relevant articles published up to December 31, 2019. Included studies were limited to original investigations assessing the association between prenatal exposure to ACEIs/ARBs and adverse pregnancy outcomes. Odds ratios were used as a summary effect measure. Pooled-effect estimates of each outcome were calculated by the random-effects meta-analysis. The main outcomes included overall and specific congenital malformations, low birth weight, miscarriage, elective termination of pregnancy, stillbirth, and preterm delivery. Of 19 included articles involving a total of 4 163 753 pregnant women, 13 studies reported an increased risk of, at least, one adverse pregnancy outcome in pregnant women who were exposed to ACEIs/ARBs. Meta-analysis revealed a significant association between overall congenital malformations and first trimester-only exposure to ACEIs/ARBs (OR = 1.94, 95% CI = 1.71-2.21, P < .0001). Cardiovascular malformations, miscarriage, and stillbirth also provided a significant relation with ACEI/ARB exposure. In conclusion, prenatal exposure to ACEIs/ARBs in the first trimester of pregnancy was found to be associated with an increased risk of adverse pregnancy outcomes. Women of reproductive age should be aware of the potential teratogenic risks of these drugs if they become pregnant.

Clinical Efficacy and Safety of Yellow Oil Formulations 3 and 4 versus Indomethacin Solution in Patients with Symptomatic Osteoarthritis of the Knee: A Randomized Controlled Trial.

BACKGROUND: Topical nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for the treatment of symptomatic osteoarthritis (OA) of the knee. However, searching for alternatives such as locally available medicinal herbs to manage OA knee pain remains of clinical value. The objective of the present study was to evaluate the efficacy and safety of two yellow oil formulations in patients with OA of the knee. METHODS: This prospective, randomized, single-blind, active-controlled, noninferiority study enrolled 102 patients with OA of the knee. Eligible patients were randomly assigned to apply either yellow oil formulation 3 (YOF3), yellow oil formulation 4 (YOF4), or indomethacin solution (INDO) topically four times daily for four weeks. Outcomes were assessed on a biweekly basis. The primary efficacy outcome measure was a 100 mm visual analog scale (VAS) of pain, while secondary endpoints included knee function, physical performance assessments, and safety parameters. Modified intention-to-treat and per-protocol analyses were applied. Assessment of noninferiority was done with a prespecified margin of 10 mm for VAS pain. RESULTS: Of 102 patients enrolled, 86 completed the study: 29/34 in the YOF3 group, 25/34 in the YOF4 group, and 32/34 in the INDO group. The absolute reduction in VAS pain at the final evaluation was -25.06 ± 13.91, -18.50 ± 16.06, and -23.38 ± 10.05 mm in the YOF3, YOF4, and INDO groups, respectively (p=0.169). Only YOF3 was found to be noninferior to INDO. Other efficacy outcomes were significantly improved in all three groups. All the interventions were well tolerated; no skin rash was observed in any of the three groups. CONCLUSIONS: YOF3 was shown to be noninferior to INDO in relieving knee pain and should be considered an alternative for the treatment of symptomatic OA of the knee. Further research into the mechanism of action of YOF3 and its long-term efficacy and safety is required.

Acute and chronic oral toxicity assessment of longan sugar extracts derived from whole fruit and from fruit pulp in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Longan (Dimocarpus longan Lour.) is one of the most popular subtropical fruits. Various parts of longan, including seeds, pericarp and pulp, have long been used in traditional medicine in China, Thailand and other Asian countries. The pulp has high sugar, vitamin and mineral content as well as bioactive components. The seeds and pericarp have also been reported to contain beneficial polyphenolic compounds. Longan sugar extract from pulp (LGSP) is prepared as a conventional sugar product. Longan sugar extract from whole longan fruit (LGSW) is also offered as a health food and as a medicinal product. AIM OF THE STUDY: The objective of this study was to identify and compare potential health hazards of both LGSW and LGSP by testing for acute and chronic oral toxicity in rats. MATERIALS AND METHODS: In acute toxicity testing, an oral dose (20 g/kg) of either LGSW or LGSP was administered to groups of rats. Mortality and clinical signs of toxicity were observed for 24 h, and then daily for a total of 14 days. In the chronic toxicity test, either LGSW (1, 2.5 and 5 g/kg/day) or LGSP (5 g/kg/day) was administered orally for a period of 180 days. After that treatment period, the rats in the satellite groups which received the highest doses of either LGSW or LGSP were observed for an additional 28 days. The rats then underwent clinical observation, body and organ weight measurement, hematological and biochemical analyses, and histopathological examination. RESULTS: In the acute toxicity study, the oral administration of LGSP or LGSW in either pellet or syrup formulations did not cause mortality or any pathological abnormalities. In the chronic toxicity study, neither LGSW nor LGSP resulted in death or in any changes in behavior of the rats. All hematological and serum biochemical values of both the LGSW- and LGSP-treated groups were within the normal ranges. No histopathological abnormalities of any internal organs were observed. CONCLUSION: The safety of longan sugar extract made from whole fruit (pulp, seeds and pericarb) is comparable to that of longan sugar extract made from pulp alone.

Effect of Short-Course Oral Ciprofloxacin on Isoflavone Pharmacokinetics following Soy Milk Ingestion in Healthy Postmenopausal Women.

Soy isoflavones have several potential benefits related to postmenopausal health. Isoflavone glycosides, found predominantly in nonfermented soy products, e.g., soy milk, require conversion by gut microbiota to their respective bioavailable aglycones prior to absorption into portal circulation. Use of short-course oral ciprofloxacin for the treatment of acute uncomplicated cystitis, the incidence of which is increasing among postmenopausal women, might adversely affect gut microbiota. The objective of this one-group pre-post treatment study was to determine the effect of short-course oral ciprofloxacin on isoflavone pharmacokinetics in healthy postmenopausal women. Eleven postmenopausal subjects were assigned to consume a single oral dose of 375 mL UHT soy milk (SOY phase). Blood samples were collected immediately before soy milk ingestion and at specific times for 32 hours after soy milk ingestion. Following a washout period of at least seven days, subjects were assigned to take 250 mg oral ciprofloxacin after breakfast and dinner for three days, followed by a single oral dose of 375 mL UHT soy milk the next day (CIPRO/SOY phase). Blood samples were collected at the same time points as in the SOY phase. Plasma samples were treated with ß-glucuronidase/sulfatase and plasma concentrations of aglycones (genistein and daidzein) were determined using high-performance liquid chromatography. Cmax, AUC0-t, and AUC0-∞ of both aglycones and Tmax of genistein obtained from the CIPRO/SOY phase were significantly lower than those obtained from the SOY phase, while Tmax of daidzein and t1/2 of both aglycones in the two phases were not significantly different.

Complete Recovery Following Electroacupuncture Therapy in Refractory Unilateral Sensorineural Hearing Loss.

Role of electroacupuncture (EA) in refractory unilateral sensorineural hearing loss (SNHL) remains unclear but might be promising for the Meniere's disease. Two cases of unilateral SNHL who were unresponsive to conventional treatment of sudden SNHL showed complete recovery after receiving EA therapy. The first case was a 46-year-old woman who received EA in the seventh month after the acute onset of sudden right hearing loss and tinnitus. She had mild-to-moderate degree of SNHL at high frequencies in the right ear with episodic vertigo. The second case was a 55-year-old woman who received EA in the sixth year after developing sudden SNHL in the right ear. Before the EA began, her pure tone average of the affected ear was 45 dB and the phonetically balanced score was 88%. The regimen for both patients included 12 sessions of EA over four weeks at the main acupoints (Tinggong (SI 19), Ermen (TE 21), Qimai (TE 18) and Yifeng (TE 17) on the affected ear and the adjuvant acupoints (Zhongzhu (TE 3), Hegu (LI 4), Qihai (CV 6), Guanyuan (CV 4), Taixi (KI 3), and Taichong (LIV 3)). Both patients regained their normal hearing thresholds three weeks after the first EA. No adverse events were observed. Hence, EA may be a useful additional therapy in unilateral SNHL, even at the late phase when other treatments have failed because the possibility of Meniere's disease cannot be excluded.

The impact of genetic polymorphisms on CYP1A2 activity in humans: a systematic review and meta-analysis.

A large interindividual variation in the activity of cytochrome P450 1A2 (CYP1A2) raises concern about therapeutic failure or toxicity when medical professionals prescribe drugs extensively metabolized by CYP1A2. To date, a number of studies have assessed the association between genetic polymorphisms and CYP1A2 activity; however, there are controversies as to the functional importance of CYP1A2 polymorphisms on the metabolism of CYP1A2 substrates. This systematic review and meta-analysis assessed the effects of genetic polymorphisms on CYP1A2 activity, as measured by caffeine metabolism, in a total of 3570 individual subjects. Higher enzyme activity was observed among those who were homozygous or heterozygous for the -163C>A polymorphism (rs762551), when compared to the wild-type individuals (SMD = 0.40, 95%CI = 0.12-0.68, p = 0.005; SMD = 0.32, 95%CI = 0.11-0.54, p = 0.003, respectively) and this was more pronounced among smokers (SMD = 0.92, 95%CI = 0.27-1.57, p = 0.005; SMD = 0.56, 95%CI = 0.22-0.90, p = 0.001, respectively). For other CYP1A2 polymorphisms, altered caffeine metabolic ratios were not seen. Our results indicate the functional importance of -163C>A polymorphism on CYP1A2 inducibility in humans.

Effect of Oral Coadministration of Ascorbic Acid with Ling Zhi Preparation on Pharmacokinetics of Ganoderic Acid A in Healthy Male Subjects: A Randomized Crossover Study.

The objective of this randomized, open-label, single-dose, two-phase crossover study was to determine the effect of ascorbic acid on pharmacokinetics of ganoderic acid A, an important biologically active triterpenoid compound with anticancer activities, following oral administration of water extract of fruiting bodies of Ling Zhi in 12 healthy male subjects. Each subject was randomized to receive either one of the two regimens: (1) a single dose of 3,000 mg of the Ling Zhi preparation or (2) a single dose of 3,000 mg of the Ling Zhi preparation in combination with 2,500 mg of ascorbic acid. After a washout period of at least two weeks, subjects were switched to receive the alternate regimen. Blood samples were collected in each phase immediately before dosing and at specific time points for 8 hours after dosing. Plasma ganoderic acid A concentrations were quantified using liquid chromatography-mass spectrometry (LC-MS). The pharmacokinetic parameters analyzed were maximal plasma concentration (Cmax), time to reach peak concentration (Tmax), area under the plasma concentration-time curve (AUC), and half-life (t1/2). An oral coadministration of ascorbic acid with Ling Zhi preparation did not significantly alter the pharmacokinetic parameters of ganoderic acid A in healthy male subjects.

Improved participants' understanding in a healthy volunteer study using the SIDCER informed consent form: a randomized-controlled study.

PURPOSE: This study aimed to evaluate the applicability of the principles and informed consent form (ICF) template proposed by the Strategic Initiative for Developing Capacity in Ethical Review (SIDCER) in a clinical pharmacokinetic study by comparing the volunteers' understanding of the enhanced ICF (developed based on the SIDCER methodology) and the conventional ICF (which was previously approved by local Ethics Committee and used in the clinical study). METHODS: A total of 550 volunteers were randomly assigned to read either the enhanced ICF or the conventional ICF (1:1) in a mock informed consent approach and subsequently performed the post-test questionnaire. The primary endpoint was the proportion of the participants who had the post-test score of ≥ 80 %; the secondary endpoints were the total score of the post-test, the score of the categorized ICF elements, and time spent for participation. RESULTS: The proportion of the participants in the enhanced ICF group who achieved the primary endpoint was significantly higher than the conventional ICF group (82.2 % vs. 60.4 %, p < 0.001). The participants in the enhanced ICF group obtained higher scores and spent less time in reading the given ICF and answering the post-test than those in the conventional ICF group (total score 19/21 vs. 18/21, p < 0.001; time spent 20 min vs. 25 min, p < 0.001). CONCLUSION: The enhanced ICF improved the understanding of the participants in this study. This demonstrates the applicability of the SIDCER ICF principles and its template in the development of an enhanced ICF for improving the quality of ICFs and subjects' understanding in clinical research. TRIAL REGISTRATION: TCTR20140727001.

Short-Term Isoflavone Intervention in the Treatment of Severe Vasomotor Symptoms after Surgical Menopause: A Case Report and Literature Review.

Isoflavones are soy phytoestrogens that potentially exert various favorable effects in postmenopausal women, for example, alleviating vasomotor episodes, attenuating bone loss, and stimulating vaginal epithelial maturation. There has, however, been lack of consensus regarding those therapeutic effects. Most clinical studies of isoflavones have been conducted with women who had undergone natural menopause, but not those who had undergone surgical menopause. This study reports on a 51-year-old woman who presented with severe vasomotor episodes after undergoing a hysterectomy and a bilateral oophorectomy due to hypermenorrhea secondary to myoma uteri. She refused hormone therapy due to fear of adverse drug reactions so was treated with oral soy isoflavones (two capsules twice daily, equivalent to at least 100 mg daily dose) for 8 weeks. The number and severity of hot flushes and her menopause-specific quality of life dramatically improved from baseline values. The serum bone resorption marker (beta C-telopeptide) decreased markedly, while vaginal epithelial maturation improved slightly, suggesting the potential of isoflavones in attenuating bone loss and stimulating vaginal maturation. The intervention did not adversely affect the hormonal profile (FSH, LH, and estradiol) and liver or renal functions. Thus, isoflavones could be an option for women experiencing severe vasomotor episodes after surgical menopause.

Efficacy of Acupuncture versus Combined Oral Contraceptive Pill in Treatment of Moderate-to-Severe Dysmenorrhea: A Randomized Controlled Trial.

This open-label randomized controlled trial was designed to compare the efficacy of acupuncture and combined oral contraceptive (COC) pill in treating moderate-to-severe primary dysmenorrhea. Fifty-two participants were randomly assigned to receive either acupuncture (n = 27) or COC (n = 25) for three menstrual cycles. Mefenamic acid was prescribed as a recue analgesic drug with both groups. The statistical approach used for efficacy and safety assessments was intention-to-treat analysis. By the end of the study, both treatments had resulted in significant improvement over baselines in all outcomes, that is, maximal dysmenorrhea pain scores, days suffering from dysmenorrhea, amount of rescue analgesic used, and quality of life assessed by SF-36 questionnaire. Over the three treatment cycles, COC caused greater reduction in maximal pain scores than acupuncture, while improvements in the remaining outcomes were comparable. Responders were defined as participants whose maximal dysmenorrhea pain scores decreased at least 33% below their baseline. Response rates following both interventions at the end of the study were not statistically different. Acupuncture commonly caused minimal local side effects but did not cause any hormone-related side effects as did COC. In conclusion, acupuncture is an alternative option for relieving dysmenorrhea, especially when COC is not a favorable choice.

Effects of the Chinese Herbal Formulation (Liu Wei Di Huang Wan) on the Pharmacokinetics of Isoflavones in Postmenopausal Women.

A combination of soy isoflavones and Liu Wei Di Huang Wan (LWDHW) is potentially effective for postmenopausal women with intolerable vasomotor episodes who are not suitable candidates for hormonal therapy. The objective of this open-label, three-phase, crossover study was to determine the influence of both single and multiple oral doses of LWDHW on isoflavone pharmacokinetics in healthy postmenopausal women. Eleven subjects were assigned to receive the following regimens in a fixed sequence with washout periods of at least one week: Phase A, a single oral dose of soy milk; Phase B, a single oral dose of soy milk coadministered with LWDHW; and Phase C, multiple oral doses of LWDHW for 14 days followed by a single oral dose of soy milk. Blood samples were collected and mixed with ß-glucuronidase/sulfatase to hydrolyze isoflavone conjugates to their respective aglycones (i.e., daidzein and genistein) and were determined using high performance liquid chromatography. The pharmacokinetic parameters analyzed were maximal plasma concentration (C max), time to reach peak concentration (T max), area under the plasma concentration-time curve (AUC), and half-life (t 1/2). The results found no statistically significant differences in pharmacokinetic parameters of daidzein and genistein among the three regimens.

Cytotoxic Effect of Coscinium fenestratum on Human Head and Neck Cancer Cell Line (HN31).

Coscinium fenestratum is widely used as a medicinal plant in many Asian countries. This study aimed to investigate the cytotoxic effect of a crude water extract of C. fenestratum (CF extract) compared to 5-fluorouracil (5-FU) on human HN31 cell line, a metastatic squamous cell carcinoma of the pharynx. The results revealed that cell morphology visualized under inverted light microscopy was changed from flat with a polygonal appearance to round appearance after CF extract application. The cell viability assay (MTT test) showed that the concentration producing 50% growth inhibition (IC50) at 48-hour incubation of CF extract on HN31 was 0.12 mg/mL, while the IC50 of 5-FU was 6.6 mg/mL, indicating that CF extract has a higher potency. However, combining various concentrations of 5-FU and CF extract at IC50 did not show synergistic effect. The CF extract dose dependently increased cell apoptosis determined by Annexin-V and propidium iodide staining. It decreased the phosphorylation of p38 MAPK and pAkt, while it increased the tumor suppressor protein p53. In conclusion, the cytotoxicity of CF extract was associated with the modulation of p38 MAPK, pAkt, and p53 signal molecules, leading to inhibiting cell survival and increasing apoptosis. No synergistic effects of CF extract and 5-FU were observed.

Analgesic, anti-inflammatory, and chondroprotective activities of Cryptolepis buchanani extract: in vitro and in vivo studies.

Cryptolepis buchanani Roem. & Schult. is widely used in folk medicine in Southeast Asia for treating muscle tension and arthritis. This study aimed to investigate an analgesic activity of the methanol extract of C. buchanani (CBE) in acetic acid-induced writhing response in mice, and to examine its anti-inflammatory activity in ethyl phenylpropiolate- (EPP-) induced ear edema and carrageenan-induced paw edema in rats. Its effects on cartilage degradation induced by interleukin-1ß (IL-1ß) in porcine cartilage explant culture were also determined. This study demonstrated that CBE significantly reduced acetic acid-induced writhing response. It also inhibited edema formation in both EPP-induced ear edema and carrageenan-induced paw edema models. In cartilage explant culture, CBE significantly reduced the sulfated glycosaminoglycan and hyaluronan released into culture media while it reserved the uronic acid and collagen within the cartilage tissues. It also suppressed the matrix metalloproteinase-2 activity with no effect on cell viability. In conclusion, CBE shows analgesic, anti-inflammatory, and chondroprotective effects in this preliminary study. Therefore, CBE may be useful as an alternative treatment for osteoarthritis.

Thai massage, and Thai herbal compress versus oral ibuprofen in symptomatic treatment of osteoarthritis of the knee: a randomized controlled trial.

The aim of this study was to verify the clinical responses to Thai massage (TM) and Thai herbal compression (THC) for treating osteoarthritis (OA) of the knee in comparison to oral ibuprofen. This study was a randomized, evaluator-blind, controlled trial. Sixty patients with OA of the knee were randomly assigned to receive either a one-hour session of TM or THC (three times weekly) or oral ibuprofen (three times daily). The duration of treatment was three weeks. The clinical assessments included visual analog scale assessing pain and stiffness, Lequesne's functional index, time for climbing up ten steps, and physician's and patient's overall opinions on improvement. In a within-group comparison, each treatment modality caused a significant improvement of all variables determined for outcome assessments. In an among group comparison, all modalities provided nearly comparable clinical efficacy after a three-week symptomatic treatment of OA of the knee, in which a trend toward greatest improvement was likely to be found in THC group. In conclusion, TM and THC generally provided comparable clinical efficacy to oral ibuprofen after three weeks of treatment and could be considered as complementary and alternative treatments for OA of the knee.

Effect of synbiotic fermented milk on oral bioavailability of isoflavones in postmenopausal women.

The purpose of this study was to investigate the effect of synbiotic fermented milk, containing Lactobacillus paracasei and inulin, on oral bioavailability and pharmacokinetics of isoflavones in healthy postmenopausal women. The study was a one-group pre-post treatment study. Twelve subjects were assigned to consume a single oral dose of 375 mL of soy beverage. Blood samples were collected immediately before and at various time points until 32 hours after the administration of the soy beverage. After a washout period, subjects were requested to consume 180 mL of synbiotic fermented milk after breakfast and dinner for 14 days, followed by a single oral dose of 375 mL of soy beverage on the next day. Collection of blood samples after the administration of the soy beverage were performed at the same time points as the former phase. Plasma isoflavone concentrations were measured by using high-performance liquid chromatography (HPLC) technique. In conclusion, this study highlighted that continuous consumption of synbiotic fermented milk followed by a single oral administration of soy beverage significantly enhanced oral bioavailability of isoflavones compared with a single oral dose of soy beverage alone.