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1.
J Pharm Pharmacol ; 68(6): 826-33, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27019348

ABSTRACT

OBJECTIVES: An anti-osteoporotic herbal formula ELP containing Epimedii Herba (E), Ligustri Lucidi Fructus (L) and Psoraleae Fructus (P) was studied to investigate the herb-herb interaction (or the possible synergistic effect) among each component and to identify the principal herbs in different modes of action. METHODS: Rat osteoblast-like UMR-106 cells proliferation, rat MSCs-derived osteoblastogenesis and RANKL-induced RAW 264.7 osteoclastogenesis were adopted to investigate the bone-forming activity and bone-degrading activity of the herbal extracts. In the statistical aspect, a modified Tallarida's approach was employed to assess the synergistic effects in herbal combinations. KEY FINDINGS: Psoraleae Fructus is the active herb for stimulating osteoblast proliferation, and mild synergy was detected in the pairwise combinations EL, LP and formula ELP. In osteoblastogenesis assay, E and L are the principal herbs for promoting osteoblast differentiation and significant synergy was detected in the pairwise combination EL. For inhibiting osteoclast formation, L is the active herb and significant synergy was detected in the 3-way combination ELP. CONCLUSIONS: The presence of E, L and P is essential for ELP formula as a whole to act against osteoporosis via enhancing bone formation and reducing bone reabsorption. An optimal dosage at 150 µg/ml was proposed for ELP based on our findings.


Subject(s)
Bone Density Conservation Agents/pharmacology , Bone Remodeling/drug effects , Drugs, Chinese Herbal/pharmacology , Epimedium , Ligustrum , Osteoblasts/drug effects , Osteoclasts/drug effects , Osteoporosis/drug therapy , Psoralea , Alkaline Phosphatase/metabolism , Animals , Bone Density Conservation Agents/isolation & purification , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/isolation & purification , Epimedium/chemistry , Ligustrum/chemistry , Male , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/pathology , Mice , Osteoblasts/metabolism , Osteoblasts/pathology , Osteoclasts/metabolism , Osteoclasts/pathology , Osteoporosis/metabolism , Osteoporosis/pathology , Phytotherapy , Plant Components, Aerial , Plants, Medicinal , Psoralea/chemistry , RANK Ligand/pharmacology , RAW 264.7 Cells , Rats , Rats, Sprague-Dawley
2.
J Ethnopharmacol ; 141(1): 250-6, 2012 May 07.
Article in English | MEDLINE | ID: mdl-22366433

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Astragali Radix (AR) and Rehmanniae Radix (RR) are two traditional Chinese medicines widely used in China for treating diabetes mellitus and its complications, such as diabetic foot ulcer. AIM OF STUDY: In our previous study, a herbal formula NF3 comprising AR and RR in the ratio of 2:1 was found effective in enhancing diabetic wound healing in rats through the actions of tissue regeneration, angiogenesis promotion and inflammation inhibition. The aims of the present study were to investigate the herb-herb interaction (or the possible synergistic effect) between AR and RR in NF3 to promote diabetic wound healing and to identify the principal herb in the formula by evaluating the potencies of individual AR and RR in different mechanistic studies. MATERIALS AND METHODS: A chemically induced diabetic foot ulcer rat model was used to examine the wound healing effect of NF3 and its individual herbs AR and RR. For mechanistic studies, murine macrophage cell (RAW 264.7) inflammation, human fibroblast (Hs27) proliferation and human endothelial cell (HMEC-1) migration assays were adopted to investigate the anti-inflammatory, granulation formation and angiogenesis-promoting activities of the herbal extracts, respectively. RESULTS: In the foot ulcer animal model, neither AR nor RR at clinical relevant dose (0.98g/kg) promoted diabetic wound healing. However, when they were used in combination as NF3, synergistic interaction was demonstrated, of which NF3 could significantly reduce the wound area of rats when compared to water group (p<0.01). For anti-inflammation and granulation formation, AR was more effective than RR in inhibiting lipopolysaccharide (LPS)-induced nitric oxide production from RAW 264.7 cells and promoting Hs27 fibroblast proliferation. In the aspect of angiogenesis promotion, only NF3 promoted cell migration of HMEC-1 cells. CONCLUSIONS: AR plays a preeminent role in the anti-inflammatory and fibroblast-proliferating activities of NF3. The inclusion of RR, however, is crucial for NF3 to exert its overall wound-healing as well as the underlying angiogenesis-promoting effects. The results of present study justified the combined usage of AR and RR in the ratio of 2:1 as NF3 to treat diabetic foot ulcer and illustrated that AR is the principal herb in this herbal formula.


Subject(s)
Angiogenesis Inducing Agents/pharmacology , Anti-Inflammatory Agents/pharmacology , Astragalus Plant , Diabetic Foot/drug therapy , Drugs, Chinese Herbal/pharmacology , Rehmannia , Wound Healing/drug effects , Animals , Astragalus Plant/chemistry , Astragalus propinquus , Cell Line , Cell Movement/drug effects , Cell Proliferation/drug effects , Diabetes Mellitus, Experimental/complications , Diabetic Foot/etiology , Diabetic Foot/immunology , Diabetic Foot/pathology , Dose-Response Relationship, Drug , Drug Synergism , Endothelial Cells/drug effects , Endothelial Cells/pathology , Female , Fibroblasts/drug effects , Fibroblasts/pathology , Humans , Inflammation Mediators/metabolism , Macrophages/drug effects , Macrophages/immunology , Mice , Neovascularization, Physiologic/drug effects , Nitric Oxide/metabolism , Phytotherapy , Plants, Medicinal , Rats , Rats, Wistar , Rehmannia/chemistry , Time Factors
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