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J Dent Res. 2019 Jan;98(1):107-116. doi: 10.1177/0022034518797275. Epub 2018 Sep 10.

Berberine Ameliorates Periodontal Bone Loss by Regulating Gut Microbiota.

Jia X1,2, Jia L1,2, Mo L1, Yuan S1,2, Zheng X1,2, He J1,2, Chen V1,3, Guo Q1, Zheng L1,4, Yuan Q1,5, Xu X1,2, Zhou X1,2.

Abstract

Postmenopausal osteoporosis (PMO) is a risk factor for periodontitis, and current therapeutics against PMO prevent the aggravated alveolar bone loss of periodontitis in estrogen-deficient women. Gut microbiota is recognized as a promising therapeutic target for PMO. Berberine extracted from Chinese medicinal plants has shown its effectiveness in the treatment of metabolic diseases such as obesity and diabetes via regulating gut microbiota. Here, we hypothesize that berberine ameliorates periodontal bone loss by improving the intestinal barriers by regulating gut microbiota under an estrogen-deficient condition. Experimental periodontitis was established in ovariectomized (OVX) rats, and the OVX-periodontitis rats were treated with berberine for 7 wk before sacrifice for analyses. Micro-computed tomography and histologic analyses showed that berberine treatment significantly reduced alveolar bone loss and improved bone metabolism of OVX-periodontitis rats as compared with the vehicle-treated OVX-periodontitis rats. In parallel, berberine-treated OVX-periodontitis rats harbored a higher abundance of butyrate-producing gut microbiota with elevated butyrate generation, as demonstrated by 16S rRNA sequencing and high-performance liquid chromatography analysis. Berberine-treated OVX-periodontitis rats consistently showed improved intestinal barrier integrity and decreased intestinal paracellular permeability with a lower level of serum endotoxin. In parallel, IL-17A-related immune responses were attenuated in berberine-treated OVX-periodontitis rats with a lower serum level of proinflammatory cytokines and reduced IL-17A+ cells in alveolar bone as compared with vehicle-treated OVX-periodontitis rats. Our data indicate that gut microbiota is a potential target for the treatment of estrogen deficiency-aggravated periodontal bone loss, and berberine represents a promising adjuvant therapeutic by modulating gut microbiota.

KEYWORDS:

butyrate; estrogen deficiency; interleukin 17A; intestinal barrier; periodontitis; postmenopausal osteoporosisPMID:30199654DOI:10.1177/0022034518797275

2018 Jul;103:1429-1435. doi: 10.1016/j.biopha.2018.04.159. Epub 2018 May 7.

Proficiencies of Zingiber officinale against spine curve and vertebral damage induced by corticosteroid therapy associated with gonadal hormone deficiency in a rat model of osteoporosis.

Zammel N1, Amri N1, Chaabane R2, Rebai T1, Badraoui R3.

Abstract

This study was assessed to examine whether Zingiber officinale (ZO) can prevent spine disorder and trabecular microarchitecture disruption in osteoporotic murin model. Three groups of male rats were selected: Controls (CTRL), combined model of osteoporosis (CMO), in which rats were orchidectomized and treated with cortisol, and CMO treated with ZO (CMO + ZO). One month after the surgical procedures, the rats were sacrificed. Lumbar curve of the spine has been evaluated using the kyphotic method. The spines were submitted to histological and histomorphometric analysis and mineral (calcium and phosphorus) metabolism assessment. Compared to CTRL, the mean kyphotic angle (KA) was significantly higher in CMO rats. The spinal deconditioning associated decreased bone trabecular volume and a disrupted microarchitecture. A disorder was observed in the serum and bone levels of calcium and phosphorus in the combined severe osteopenia model. An increase in the level of TRAcP associated with an increase in osteoclast number and activity has been reported. These disturbances were reduced following the use of ZO in the CMO + ZO group. Finally, ginger might be an alternative therapeutic candidate for the treatment of severe osteopenia induced vertebral damage and spine curve disruption.Copyright © 2018 Elsevier Masson SAS. All rights reserved.

KEYWORDS:

Osteoporosis; Spine curve; Vertebral damage; Zingiber officinale

PMID:
29864927
DOI:
10.1016/j.biopha.2018.04.159
2015 Oct;30(10):1905-13. doi: 10.1002/jbmr.2513. Epub 2015 May 10.

Cannabidiol, a Major Non-Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts.

Kogan NM1, Melamed E1, Wasserman E1, Raphael B1,2, Breuer A3, Stok KS4, Sondergaard R4, Escudero AV4, Baraghithy S1, Attar-Namdar M1, Friedlander-Barenboim S5, Mathavan N6,7, Isaksson H6,7, Mechoulam R3, Müller R4, Bajayo A1, Gabet Y2, Bab I1.

Abstract

Cannabinoid ligands regulate bone mass, but skeletal effects of cannabis (marijuana and hashish) have not been reported. Bone fractures are highly prevalent, involving prolonged immobilization and discomfort. Here we report that the major non-psychoactive cannabis constituent, cannabidiol (CBD), enhances the biomechanical properties of healing rat mid-femoral fractures. The maximal load and work-to-failure, but not the stiffness, of femurs from rats given a mixture of CBD and Δ(9) -tetrahydrocannabinol (THC) for 8 weeks were markedly increased by CBD. This effect is not shared by THC (the psychoactive component of cannabis), but THC potentiates the CBD stimulated work-to-failure at 6 weeks postfracture followed by attenuation of the CBD effect at 8 weeks. Using micro-computed tomography (μCT), the fracture callus size was transiently reduced by either CBD or THC 4 weeks after fracture but reached control level after 6 and 8 weeks. The callus material density was unaffected by CBD and/or THC. By contrast, CBD stimulated mRNA expression of Plod1 in primary osteoblast cultures, encoding an enzyme that catalyzes lysine hydroxylation, which is in turn involved in collagen crosslinking and stabilization. Using Fourier transform infrared (FTIR) spectroscopy we confirmed the increase in collagen crosslink ratio by CBD, which is likely to contribute to the improved biomechanical properties of the fracture callus. Taken together, these data show that CBD leads to improvement in fracture healing and demonstrate the critical mechanical role of collagen crosslinking enzymes.© 2015 American Society for Bone and Mineral Research.
PMID:
25801536
DOI:
10.1002/jbmr.2513
2014 Jul;34(7):577-84. doi: 10.1016/j.nutres.2014.07.002. Epub 2014 Jul 8.

Six weeks daily ingestion of whole blueberry powder increases natural killer cell counts and reduces arterial stiffness in sedentary males and females.

McAnulty LS1, Collier SR2, Landram MJ2, Whittaker DS3, Isaacs SE4, Klemka JM4, Cheek SL4, Arms JC2, McAnulty SR2.

Abstract

Evidence suggests that berries contain bioactive compounds, which reduce certain cancers and hypertension. Our hypothesis was that daily blueberry (BB) consumption would increase natural killer (NK) cells and plasma redox capacity and reduce blood pressure, augmentation index (AIx), central pulse wave velocity, and aortic systolic pressures (ASPs). Twenty-five men and postmenopausal women aged 18 to 50 years were recruited and randomized to BB (n, 13) or placebo groups (n, 12). Participants were provided with BB (equivalent to 250 g berries) or placebo powders each day for 6 weeks. Blood pressure, vascular performance testing, and blood samples were taken at baseline (presupplementation). Participants returned after 6 weeks and repeated all procedures. Presupplementation to postsupplementation comparisons for the main effects of treatment, time, and treatment-time interaction were made using a 2 (treatment) × 2 (times) repeated-measures analysis of variance for all vascular measures, redox status, and NK cell counts. Anthropometric measures were compared using t tests. Body mass, composition, and overall blood pressures were not affected in either group. Overall, AIx and ASPs were decreased in BB (treatment effect, P = .024 and P = .046, respectively). Plasma redox was not affected. Absolute NK cells were increased in BB (time, P = .001 and interaction, P = .012). Subjects (n, 9) with prehypertensive pressures (≥120/80 mm Hg, respectively) were examined as a subset using t tests and exhibited significant reductions in diastolic pressure (P = .038) from presupplementation to postsupplementation in BB. We conclude that BB ingestion for 6 weeks increases NK cells and reduces AIx, ASP, and diastolic pressures in sedentary males and females.
2012 Jun;18(6):583-8. doi: 10.1089/acm.2011.0202.

Influence of a specific ginger combination on gastropathy conditions in patients with osteoarthritis of the knee or hip.

Drozdov VN1, Kim VA, Tkachenko EV, Varvanina GG.

Abstract

BACKGROUND:

Nonsteroid anti-inflammatory drugs represent an important osteoarthritis (OA) therapy component, but also a leading cause of gastropathy: one of the most frequent and serious OA therapy complications. The aim of the present study was to study the influence of GI health in an OA population receiving either ginger or diclofenac.

METHODS:

Forty-three (43) patients with confirmed OA (knee and hip) were included in a randomized controlled study. A ginger group of 21 patients (17 women, 4 men) was given a specific ginger combination daily (340 mg EV.EXT 35 Zingiber officinalis extract) for 4 weeks. A diclofenac group (positive control) of 22 patients (18 women, 4 men) received 100 mg diclofenac daily for the same period. Both groups also received 1000 mg glucosamine daily. Gastrointestinal pain and dyspepsia were evaluated according to the severity of dyspepsia assessment (SODA) form. Patients also underwent esophagogastroduodenoscopy (EGDS) including biopsy before and after the treatment. Serum gastrin-17 levels, and stomach mucosa prostaglandins (PG) E1, E2, F2α, and 6-keto PGF1α (PGI2) levels were measured. Arthritic pain was evaluated using the visual analogue scale (VAS) on standing and moving.

RESULTS:

The ginger group showed a slight but significantly lowered SODA pain and no change of SODA dyspepsia. EGDS showed significantly increased levels of PGE1, PGE2, and PGF2α in the stomach mucosa. This rise in gastric mucosa PG levels correlated with an increase in serum gastrin-17. On the other hand, the diclofenac group showed increased SODA pain and dyspepsia values with a corresponding significant decrease of stomach mucosa prostaglandins and general negative stomach mucosa degeneration. Both groups showed a relevant and significantly lowered VAS pain both on standing and moving.

CONCLUSIONS:

The ginger combination is as effective as diclofenac but safer in treating OA, being without effect on the stomach mucosa. The increased mucosal PGs synthesis in the ginger group supports an increased mucosa-protective potential. VAS; visual analogue scale, 0-100 mm.

PMID:
22784345
DOI:
10.1089/acm.2011.0202
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