New oligomeric neolignans from the leaves of Magnolia officinalis var. biloba.

Six new oligomeric neolignans including two trimeric neolignans (1 and 2) and four dimeric neolignans (3-6) were isolated from the leaves of Magnolia officinalis var. biloba. Their structures were determined based on HR-ESIMS and NMR data, as well as electronic circular dichroism (ECD) calculations. Compound 1 is formed from two obovatol moieties directly linked to an aromatic ring of the remaining obovatol moiety, which is an unprecedented type of linkage between monomers. All isolates were assessed for their inhibitory effects on NO production in LPS-stimulated RAW 264.7 macrophage cells. Compounds 1 and 3 showed significantly inhibitory activities with IC50 values of 6.04 and 3.26 µmol·L-1, respectively.

New lignans and acetophenone derivatives with α-glucosidase inhibitory activity from the leaves of Melicope patulinervia.

Four new lignans, patulinones A-D (1-4) and three new acetophenone derivatives, patulinones E-G (5-7) were isolated from the leaves of Melicope patulinervia. Their structures were elucidated on the basis of the interpretation of HR-ESIMS, NMR, CD data. All the isolated compounds were evaluated for α-glucosidase inhibitory activity. Of the isolates, compound 4 was found to exhibit the strongest inhibition against α-glucosidase with IC50 value of 6.02 ± 0.46 µM.

Positive Effects of Qing'e Pill () on Trabecular Microarchitecture and its Mechanical Properties in Osteopenic Ovariectomised Mice.

OBJECTIVE: To investigate the impact of Qing'e Pill (, QEP) on the cancellous bone microstructure and its effect on the level of ß-catenin in a mouse model of postmenopausal osteoporosis. METHODS: Ninety-six 8-week-old specific pathogen free C57BL/6 mice were randomly divided into 4 groups (24/group): sham, ovariectomised osteoporosis model, oestradiol-treated, and QEP-treated groups. Three months after surgery, the third lumbar vertebra and left femur of the animals were dissected and scanned using micro-computed tomography (micro-CT) to acquire three-dimensional (3D) parameters of their cancellous bone microstructure. The impact of ovariectomy, the effect of oestradiol and QEP intervention on cancellous bone microstructure, and the expression of ß-catenin were evaluated. RESULTS: The oestradioland the QEP-treated groups exhibited a significant increase in the bone volume fraction, trabecular number, trabecular thickneßs, bone surface to bone volume ratio (BS/BV), and ß-catenin expression compared with those of the model group (P <0.05). In contrast, the structure model index, trabecular separation, and BS/BV were significantly decreased compared with those of the ovariectomised osteoporosis model group (P <0.05). No differences were observed in the above parameters between animals of the QEP- and oestradiol-treated groups. CONCLUSIONS: The increased ß-catenin expression may be the mechanism underlying QEP's improvement of the cancellous bone microstructure in ovariectomised mice. Our findings provide a scientific rationale for using QEP as a dietary supplement to prevent bone loss in postmenopausal women.

Effects of Modified Qing'e Pill () on expression of adiponectin, bone morphogenetic protein 2 and coagulation-related factors in patients with nontraumatic osteonecrosis of femoral head.

OBJECTIVES: To observe the regulation of Chinese herbal medicine, Modifified Qing'e Pill (, MQEP), on the expression of adiponectin, bone morphogenetic protein 2 (BMP2), osteoprotegerin (OPG) and other potentially relevant risk factors in patients with nontraumatic osteonecrosis of the femoral head (ONFH). METHODS: A total of 96 patients with nontraumatic ONFH were unequal randomly divided into treatment group (60 cases) and control group (36 cases). The treatment group were treated with MQEP while the control group were treated with simulated pills. Both groups were given caltrate D. Six months were taken as a treatment course. Patients were followed up every 2 months. The levels of plasma adiponectin, BMP2, OPG, von Willebrand factor (vWF), von Willebrand factor cleaving protease (vWF-cp), plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA), C-reactive protein (CRP), blood rheology, bone mineral density (BMD) of the femoral head and Harris Hip Score were measured before and after treatment. RESULTS: After 6 months of treatment, compared with the control group, patients in the treatment group had signifificantly higher adiponectin and BMP2 levels (P<0.01 and P=0.013, respectively), lower vWF, PAI-1 and CRP levels (P=0.019, P<0.01 and P<0.01, respectively), and lower blood rheology parameters. BMD of the femoral neck, triangle area and Harris Hip Score in the treatment group were signifificantly higher than those in the control group. Moreover, plasma adiponectin showed a positive association with BMP2 (r=0.231, P=0.003) and a negative association with PAI-1 (r=-0.159, P<0.05). CONCLUSION: MQEP may play a protective role against nontraumatic ONFH by increasing the expression of adiponectin, regulating bone metabolism and improving the hypercoagulation state, which may provide an experimental base for its clinical effects.

Effect of Qing'e formula on circulating sclerostin levels in patients with postmenopausal osteoporosis.

Serum sclerostin is positively associated with serum 25 hydroxyvitamin D concentration. Our preliminary studies confirmed that Qing'e formula (QEF) could effectively increase serum 25 hydroxyvitamin D concentration in patients with postmenopausal osteoporosis (PMOP), but the effect of supplementation with QEF on serum sclerostin is unknown. This study investigated the effects of supplementation of QEF on serum sclerostin levels in patients with PMOP. Totally 120 outpatients and inpatients with PMOP treated in our hospital between January and October 2012 were randomly divided into QEF+calcium group, alfacalcidol+calcium group, and placebo+calcium group (n=40 each), with a follow-up period of 2 years. The serum levels of sclerostin, 25 hydroxyvitamin D, and bone turnover markers (ß-CTX, N-MID and T-PINP) at baseline and at the 6th month, 1st year, 1.5th year, and 2nd year after treatment were measured. The results showed that the levels of circulating sclerostin were increased significantly at the 6th month after treatment in QEF+calcium group and alfacalcidol+calcium group as compared with placebo+calcium group (P<0.05), but there was no significant difference between the former two groups (P>0.05). The levels of ß-CTX, N-MID and T-PINP in serum were decreased in both QEF+calcium group and alfacalcidol+calcium group at the 6th month after treatment, without significant difference between the two groups (P>0.05). But the levels were significantly lower than that in placebo+calcium group (P<0.05). These results suggest that the mechanism by which QEF modulates bone metabolism in patients with PMOP might be related with the effect of QEF in increasing sclerostin expression. Our findings provide a scientific rationale for using QEF as an effective drug to prevent bone loss in PMOP.

[Clinical research on warm acupuncture therapy for pain in postmenopausal osteoporosis].

OBJECTIVE: To observe the clinical efficacy on pain in postmenopausal osteoporosis treated with the warm acupuncture therapy and discuss its effect mechanism. METHODS: Ninety cases of postmenopausal osteoporosis were randomized into a warm acupuncture group, an electroacupuncture group and a medication group, 30 cases in each group. In the warm acupuncture group and the electroacupuncture group, Dazhu (BL 11), Shenshu (BL 23) and Xuanzhong (GB 39) were selected bilaterally and stimulated with the warm acupuncture and electroacupuncture therapies respectively, once a day for 30 days totally. In the medication group, caltrate-D tablets were prescribed, 600 mg, once a day for 30 days totally. The changes in the bone density T value, visual analogue scale (VAS) score, serum insulin like growth factor 1 (IGF-1), interleukin 6 (IL-6) and tumor necrosis factor (TNF-alpha) were observed before and after treatment in the three groups. RESULTS: (1) The bone density T value in the patients of postmenopausal osteoporosis did not change obviously after 30 days treatment with the three therapies; (2) VAS score was all reduced after treatment, in which, the result in the warm acupuncture group was the most obvious (6.73 +/- 0.24 before treatment vs 4.43 +/- 0.26 after treatment). The value after treatment in the warm acupuncture group was different significantly as compared with the electroacupuncture group (5.13 +/- 0.31) and the medication group (5.17 +/- 0.33, both P < 0.05). (3) The level of serum IGF-1 was improved after treatment in the warm acupuncture therapy [(119.5 +/- 20.1) ng/mL before treatment vs (156.5 +/- 23.9) ng/mL after treatment], which was more apparent as compared with the electroacupuncture group [(136.3 +/- 24.5) ng/mL] and the medication group [(127.7 +/- 22.1) ng/mL, all P < 0.05]. Concerning to reducing the levels of IL-6 and TNF-alpha in serum, the results in the warm acupuncture group were superior to the other two groups (all P < 0.05). CONCLUSION: The warm acupuncture therapy achieves the significant efficacy on pain in postmenopausal osteoporosis, which could be related to increasing the level of IGF-1, decreasing the levels of IL-6 and TNF-alpha, promoting bone formation and inhibting bone absorption.

[Effect of acupoint heat-sensitive moxibustion intervention on serum osteopontin and matrix metalloproteinase-3 in patients with acute knee pain].

OBJECTIVE: To observe the clinical effect of acupoint heat-sensitive moxibustion for acut knee arthralgia and to analyze its effect on serum osteopontin (OPN) and matrix metalloproteinase-3 (MMP-3) contents in patients with knee osteoarthritis so as to study its mechanism underlying improving arthralgia. METHODS: One hundred and forty-four patients with acute knee knee osteoarthritis were randomly allocated to acupoint heat-sensitive moxibustion (moxibustion), electroacupuncture (EA) and medication groups. Patients of the moxibustion group were treated by suspended moxibustion over bilateral Weizhong (BL 40) for 40 min each point, once daily for 15 days. Patients of the EA group were treated by EA stimulation of Neixiyan (EX-LE 4), Dubi (ST 35), Xuehai (SP 10) and Liangqiu (ST 34) for 30 min, once daily for 15 days; and those of the medication group treated by oral administration of Sanqi Tongshu capsules (Panax Notoginseng, etc. used for promoting blood circulation and removing blood stasis), 3 times daily for 15 days. Serum OPN and MMP-3 levels were detected with ELISA. RESULTS: Following the treatment, of the 50, 50 and 44 cases in the moxibustion, EA and medication groups, 24, 20 and 14 were excellent, 18, 16 and 13 were good in therapeutic effect, 7, 4, and 3 were effective, and 1, 10, and 14 invalid, with the excellent and good rates being 84%, 72.0% and 61.4%, respectively. Serum OPN content of the moxibistion and EA groups, and serum MMP-3 content of the moxibustion group were reduced considerably in comparison with pre-treatment in the same one group (P < 0.01), while serum OPN level of the medication group and MMP-3 of the EA group were decreased slightly. The effect of moxibustion was evidently superior to that of medication in lowering serum OPN level (P < 0.05) and superior to that of both EA and medication in lowering serum MMP-3 content (P < 0.05). CONCLUSION: Acupoint heat-sensitive moxibustion has a good therapeutic effect in relieving acute knee arthralgia, which may be related to its effects in decreasing serum OPN and MMP-3 levels.