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Biochemical and hormonal evaluation of Cissus quadrangularis in accelerating healing process of bone fracture: A clinical study
Abstract
Repair of bone defects secondary to trauma, osteoporosis, osteomyelitis and fracture nonunion poses a significant problem for many orthopedicians. As a part of our continuing screening of biologically active natural fracture healing accelerating agents, drug Asthishrunkhala reported to contain phytoestrogenic steroids, ascorbic acid, carotene, calcium, and anabolic steroids and shown to heal the bone fractures in several in vivo studies. Therefore, a random controlled study was conducted with the aim to evaluate the effective remedial therapy to accelerate bone healing so as to rehabilitate the individual as early as possible. Fracture healing was assessed with biochemical parameters like serum calcium, serum phosphorus and a hormonal parameter PTH (parathyroid hormone) and their values were evaluated during fracture healing. From the assessed data it was found that bone healing process was accelerated as serum level of PTH Hormone have shown increasing trend during the period of 31 days and it was at its peak on 21st day from inception of administration of drug; but levels of calcium and phosphorus were remain maintained during period of fracture healing. In control group it was observed that serial values of Serum Calcium, Serum Phosphorus and PTH Hormone were not having significant fluctuations. This indicates that the process of fracture healing or osteoblastic activity was initiated earlier in trial group. Hence study concludes that the drug Cissus quadrangularis is having influence on accelerating the fracture healing process and further it helps in reducing period of immobilization and early rehabilitation.
... A total of 1108 patients using Cissus in three different indications including hemorrhoids, obesity/overweight, and bone fractures were included in our review. Four studies involving 784 patients with hemorrhoids were conducted in Thailand (Rojanawiwat 2010, Lekutai and Pirshahid 2011, Panpimanmas et al. 2011, Kanket et al. 2012, while three studies involving 160 patients with bone fractures were conducted in India (Siddaram et al. 2012, Singh et al. 2013, Lingram et al. 2014. The remaining studies involving 164 obese/overweight persons were conducted in Cameroon (Oben et al. 2006, Oben et al. 2008. ...
... The remaining studies involving 164 obese/overweight persons were conducted in Cameroon (Oben et al. 2006, Oben et al. 2008. Two studies were designed as open label (Siddaram et al. 2012, Lingram et al. 2014) while the others were double blinded. Follow-up durations for hemorrhoid therapy were 1 to 2 weeks whereas those for bone fractures and obesity/overweight were 4 to 8 weeks, and 6 to 10 weeks, respectively. ...
... Most were female and aged 24-60 years. In three studies, patients aged 12-70 years who had bone fractures on various sites were included (Siddaram et al. 2012, Singh et al. 2013, Lingram et al. 2014. In two studies, obese/overweight persons with aged 19-54 years were included (Oben et al. 2006, Oben et al. 2008. ...
Cissus quadrangularis L. (Cissus) is a medicinal plant commonly used for centuries for various conditions, but lacks critical appraisal of its clinical effects. This study aimed to determine the efficacy and safety of Cissus in all conditions. Publications from 12 electronic databases were searched from inception through November 2016. A total of nine studies with 1108 patients were included. Each outcome was pooled using a random effects model. Effects of Cissus on hemorrhoid symptoms were not different from any comparators but had significant effects on bone pain. Effects of Cissus combination products on body weight reduction, low-density lipoprotein, triglyceride, total cholesterol, and fasting blood sugar were superior to placebo, with weighted mean difference of -5.19 kg (-8.82, -1.55), -14.43 mg/dl (-20.06, -8.80), -37.50 mg/dl (-48.71, -26.29), -50.50 mg/dl (-70.97, -30.04), and -10.39 mg/dl (-14.60, -6.18), respectively. No serious adverse effects were reported. Quality of evidence based on Grades of Recommendations Assessment Development and Evaluation (GRADE) indicated low (bone fractures) to high quality (hemorrhoids, body weight reduction).In conclusion, Cissus had benefit for bone fractures, but not for hemorrhoids. For obesity/overweight, only combination products are pooled and show benefit. However, high-quality studies remain needed. Copyright © 2017 John Wiley & Sons, Ltd.
... In the CQ-treated group, early onset of fracture healing or osteoblastogenesis lead to early recovery as compared to placebo group. Also, increased serum parathyroid hormone (PTH) levels were observed with CQ treatment, which is known to enhance bone healing [28] . In another such comparative study, 100 subjects admitted for various fractures were evaluated, with half of subjects receiving CQ treatment and half without CQ. ...
... The safety profile of oral CQ administration for the longest period to date (24 weeks) was reported in this study. The participants reported good tolerance, and the most frequently found AE was gastrointestinal upset, which is consistent with previous studies (Lingram et al., 2014;Oben et al., 2006Oben et al., , 2008Panpimanmas et al., 2010). This AE can be reduced after consuming a meal. ...
Background
: Osteopenia refers to bone density that is not normal but also not as low as that noted in osteoporosis. Osteopenia leads to osteoporosis and increases the risk of fractures. Current research is focused on agents that will prevent or slow the progression of bone loss. On the basis of published evidence, Cissus quadrangularis (CQ) might potentially provide a novel natural treatment for osteopenia.
Purpose
: To determine the effect of 24 weeks of consecutive treatment with CQ on delaying bone loss and safety in postmenopausal women (PMW) with osteopenia.
Methods
: This study is a randomized, placebo-controlled trial. Here, 134 enrolled PMW with osteopenia (>40 years and having no period for 1–10 years) received CQ at 1.2 (CQ1.2) or 1.6 g/day (CQ1.6) or placebo. The % change in bone mineral density (BMD) at the lumbar spine (L1–L4), femoral neck, and total hip served as the primary outcome. The %change in bone turnover markers (BTMs), including C-terminal telopeptide of type I collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP), was the secondary outcome. These outcomes were compared between the CQ vs. placebo group at weeks 12 and 24. The least significant change (LSC) was used to monitor clinical changes. The adverse events (AE) were monitored.
Results
: A total of 108 participants completed this study. The %BMD changes in the CQ-treated groups did not differ at any site after 24 weeks compared to the placebo. Statistically significant differences were detected in CQ1.6 at the lumbar spine (0.011±0.025 g/cm², p=0.008) and CQ1.2 at the femoral neck (–0.015±0.036 g/cm², p=0.024) compared to baseline, but these changes did not exceed the LSC. Reduced bone remodeling activity was detected in both CQ-treated groups. Compared to the placebo, the %P1NP change was significantly reduced in CQ1.6 (–2.46±26.05%; p<0.01) at week 12 and in CQ1.2 (–3.36±29.47%; p<0.01) and CQ1.6 (–9.95±22.22%; p<0.01) at week 24. These results correlated with the within-group comparison, which showed a continuously significant increase in both BTMs in the placebo group. However, a stable CTX and a significant reduction in P1NP (p<0.05) were detected in both CQ-treated groups. This reduction exceeded the LSC of P1NP. The incidence of adverse events did not differ among the three groups.
Conclusion
: This is the first clinical report that showed a promising effect on delaying bone loss of orally administration of CQ for 24 weeks, as indicated by a slower bone remodeling process via a reduction in BTMs. However, no change in BMD was observed.
... However, Singh et al. 27 while comparing CQ, Moringaoleifera, and Osteoseal in mandibular fractures, showed an insignificant increase in calcium levels in the CQ group. A similar insignificant increase in calcium results was found by Rasale et al. 28 while evaluating CQ in long bone fractures. ...
Study Design
Randomized Control Trial.
Objectives
A randomized control trial was planned to aim to assess whether subcutaneous Injection of Teriparatide and Tablet Reunion (combination of Cissus Quadrangularis and Dalbergia sissoo) improves maxillofacial fracture healing as compared to the control group.
Methods
24 patients of mandibular fracture with or without concomitant maxillofacial fractures were randomly divided into 3 equal groups (Group 1- Control, Group 2- Tablet Reunion, and Group 3- Injection Teriparatide) and the treatment duration was 4 weeks. Pain, fracture site mobility, bite force, serum markers, and radiographic healing were assessed preoperatively and postoperatively at regular intervals till 12 weeks.
Results
Group 2 showed early pain relief, although it was insignificant. Group 3 showed the highest anterior bite force at all the time points. Change in mean posterior bite force (PBF) showed a statistically significant increase at 8th week and 12th week in intergroup comparison; however, at 12th week, Group 3 was significantly better than Group 1 and reported the highest posterior bite force compared to other groups. Serum calcium and PTH level showed no significant difference, whereas Serum ALP showed a statistically significant increase in Group 3. The radiographic assessment showed no significant difference among the 3 groups.
Conclusion
Both the intervention group drugs showed a promising effect on accelerating the fracture healing and improving bite force restoration with the osteoanabolic action; however, early radiographic healing and increased serum osteogenic markers in Group 3 indicate its possible optimistic role in maxillofacial fracture healing.
... The stems of CQ have been reported to contain various biological activitiese.g. antioxidative as well as antimicrobial activities [5], antinociceptive potential [6], abilities to protect and heal peptic ulcers [7], induction of weight loss in obese subjects [8], properties such as an anticonvulsant, an analgesic, a smooth muscle relaxant [9], activities against hemorrhoids [10] as well as atherosclerosis [11], and acceleration of bone fracture healing [12,13]. However, the effects of CQ on bone are more prominent than others. ...
Background:
Cissus quadrangularis Linn. (CQ) has been used in Indian and Thai traditional medicine for healing bone fractures because of numerous active ingredients in CQ. It is still unclear which compounds are the active ingredients for bone formation.
Methods:
The molecular docking technique, the ethanolic extraction along with hexane fractionation, and an in vitro experiment with a human osteoblast cell line (MG-63) were used to narrow down the active compounds, to prepare the CQ extract, and to test biological activities, respectively.
Results:
The molecular docking technique revealed that quercetin and β-sitosterol had highest and lowest potential to bind to estrogen receptors, respectively. Compared to the crude ethanol extract (P1), the ethanolic fraction (P2) was enriched with rutin and quercetin at 65.36 ± 0.75 and 1.06 ± 0.12 mg/g, respectively. Alkaline phosphatase (ALP) activity was significantly enhanced in osteoblasts exposed to the P2 in both tested concentrations. The amount of hydroxyproline was slightly increased in the P1 treatment, while osteocalcin was inhibited. Moreover, the P2 significantly activated osteoprotegerin (OPG) and inhibited receptor activator of nuclear factor κ ligand (RANKL) expression.
Conclusions:
Taken together, the enriched rutin and quercetin fraction of CQ triggered the molecules involved in bone formation and the molecules inhibiting bone resorption.
... In single blind clinical controlled human trial, serum PTH level was in peak at 21 st day of fracture healing, osteoblastic activity was also maximum at the end of third week as evidenced in animals. It is also having influence on accelerating the fracture healing process and further it helps in reducing period of immobilization and early rehabilitation 10 . ...
The objective of this research was to analyse the gastroprotective effect of Cissus quadrangularis extract (CQE) along with its mechanism underlying the therapeutic action against the gastric mucosal damage induced by aspirin. In this study, we investigated the effect of CQE on the course of experimentally induced gastric ulcer by analyzing the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), microvascular permeability, activity of nitric oxide synthase-2 (NOS-2), mitochondrial antioxidants, lipid peroxidation and DNA damage. A significant increase in vascular permeability, NOS-2 activity, TNF-alpha, IL-1beta levels and oxidative damage were noted in aspirin administered rats. Pretreatment with CQE (500 mg/kg bw/day) by oral gavage for 7 days significantly attenuated these biochemical changes caused by aspirin in rats. Tissue damage was showed by decreased levels of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) and an associated rise in lipid peroxidation (LPO) in mitochondria, which were reversed by CQE. In addition, CQE prevents oxidative damage of DNA by reducing DNA fragmentation indicating its block on cell death. Ulcer protection in CQE treated rats was confirmed by histoarchitecture, which was comprised of reduced size of ulcer crater and restoration of mucosal epithelium. Thus, reduced neutrophil infiltration, antiapoptotic and antioxidant action have a pivotal role in the gastroprotective effect of CQE.
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Vagbhata, Ashtang Hridya, Vidyotini Tika commentary of Kaviraj
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