Learn more about Cissus Quadrangularis uses, effectiveness, possible side effects, interactions, dosage, user ratings and products that contain Cissus. Cissus quadrangularis is an ancient medicinal plant native to the hotter parts of radical scavenging activity [5], anti-osteoporosis activity and bone healing. Cissus quadrangularis L. (veld grape) is a climber plant of Vitaceae family. A case Keywords: Cissus quandranglis; Bone healing; Fracture;.

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To receive news and publication updates for Journal of Osteoporosis, enter ciissus email address in the box below. This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Women drastically loose bone during and after menopause leading to osteoporosis, a disease characterized by low bone mass increasing the risk of fractures with minor trauma.

Existing therapies mainly reduce bone resorption, however, all existing drugs have severe side effects. Recently, the focus is to identify alternative medicines that can prevent and treat osteoporosis with minimal or no side effects. Two-month old mice were either sham operated or ovariectomized and fed CQ quadraangularis.

In the distal femoral metaphysis, femoral diaphysis, and proximal tibia, control mice had decreased cancellous and cortical bone, while CQ-fed mice showed no significant differences in the trabecular number, thickness, and connectivity density, between Sham and OVX mice, except for cortical bone mineral content in the proximal tibia. T were no changes in the bone at the tibio-fibular junction between groups.


We conclude that CQ effectively inhibited bone loss in the cancellous and cortical bones of femur and proximal tibia in these mice.

Osteoporosis is a disease associated with aging that causes fragility of bones making them susceptible to fractures with minor trauma.

Bone is a dynamic organ that undergoes lifelong changes by bone remodeling using specialized cells and cissuz the predominant process after attaining peak bone mass around the third decade. Csisus is an essential process for maintaining the skeleton by repairing any damaged portions and removal of old bone as well as for discharging calcium and phosphorus from bone stores to maintain ionic homeostasis in the body.

An imbalance in the process of bone remodeling where there is increased bone resorption alone or in combination with decreased bone formation results in net loss of bone. After attaining peak bone mass during the third decade, humans start losing bones at the rate of 0. In case of women, during menopausal age, there is drastic loss of bone. Currently, there are cissud different groups of agents that are used to treat and prevent osteoporosis. But the risks of side effects caused by these drugs are severe [ 1 — 4 ].

This has, recently, led to the search for alternative medicines to treat and prevent osteoporosis. Different cultures around the world have used herbs for thousands of years to treat several health conditions. One of the herbs that have shown beneficial effects on bone belongs to the Cissus family of plants.

Cissus quadrangularis CQ is a medicinal herb used in Siddha and Ayurvedic medicine since ancient times in Asia, as a general tonic and analgesic, especially for bone fracture healing [ 5 ].

Recently, CQ has been linked to several health benefits such as antiobesity [ 6 ], reduction of proinflammatory cytokines [ 7 ], anti-inflammatory [ 8 ], antioxidant [ 9 ], antiglucocorticoid [ 10 ], and antidiabetic properties [ 11 ].

The study has further demonstrated that in the presence of CQ, bone mineralization takes place much earlier, when compared to that seen in its absence [ 13 ]. During bone mineralization, accumulation of mucopolysaccharides precedes the actual mineralization process and CQ increased mucopolysaccharides at the site of fracture [ 14 ].

CQ also increased calcium uptake and mechanical properties of bone in rats when compared to that of the controls [ 15 ]. More recently, Shirwaikar et al. Petroleum ether extracts of CQ stimulated osteoblastogenesis and mineralization in bone marrow mesenchymal cells and murine osteoblastic cell lines [ 1718 ]. In the present study, we determined the effects of CQ on postmenopausal bone loss in the long bones of female mice.

Both techniques give different measurements and they complement each other. We also tested some bone biochemical markers and proinflammatory cytokines in the serum. When mice were eight weeks of age, they were either sham operated or ovariectomized. After one month, mice were divided into the following groups: Mice were maintained in the dietary regimens for eleven weeks and sacrificed. Mice were weighed regularly. At the time of sacrifice, body weight was recorded.


In the proximal tibial metaphysis PTM and distal femoral metaphysis DFMboth cancellous and cortical bone surrounding the cancellous bone were scanned and analyzed. The following parameters were determined for both sites: One slice was scanned at the FD mid-diaphysis and at the TF junction for measuring pure cortical bone and the following parameters determined: Concord, CA at 20 microns.

Each scan consisted of slices with an exposure time of 30 seconds per slice. Newman-Keuls multiple comparison test was used to analyze the differences between groups for significance. No significant changes were seen in the weights of the spleen and kidney Table 1. No significant differences were observed in the liver, spleen and kidneys weights Table 1. Uterus was carefully examined for any changes and no visible changes were seen.

Although there was an increase in the cytokines that were measured in the LC O mice these increases were not statistically significant between the different groups Table 2. Cissus quadrangularis belongs to the vitaceae family and is found in South East Asia where it is edible and is used as a vegetable.

This plant has been used from ancient times to enhance fracture healing and has several other health benefits including antiinflammatory [ 8 ], antiglucocorticoid [ 10 ], antidiabetic [ 11 ] antibacterial [ 521 ], and antioxidant properties [ 9 ]. This plant has triterpenoids [ 2223 ], steroids [ 2224 ] stilbenes [ 25 ], flavanoids [ 13 ], lipids [ 13 ], and several catalpols [ 13 ].

Slowly, interest in natural products for the treatment and prevention of disease is growing in the quest to minimize severe side effects that existing drugs can cause and WHO has endorsed the safe and effective use of such medicines [ 26 ]. We studied the effects of CQ-dried powder stems and leaves cizsus an animal model for postmenopausal bone loss.

Although CQ by itself did not increase bone mass we observed that it decreased bone loss in the distal femoral metaphysis and proximal tibial metaphysis regions of the long bones that have both cancellous and cortical bones. Loss of cancellous bone from these regions is typical after ovariectomy and menopause, mainly because endocortical resorption is stimulated.

Bone protection in the distal femur and proximal tibia is mainly due to decreased bone resorption at the endocortical bone surface and preservation of trabecular microarchitecture. This is supported by the well preserved trabecular morphology in the CQ O mice Figure 5 and data is in line with reports using CQ ethanol extracts. When young Wistar rats were fed CQ ethanol extracts, after ovariectomy for three months, there was restoration of architecture and increased biomechanical properties in the femur [ 16 ].

However, this is the first report to show the effects of CQ on bone using densitometric morphometric analyses including actual BMD and BMC values for the different bone sites. Moreover, we have tested several bone sites femoral and tibial metaphysis as well as femoral and tibial diaphysis as it is well known that different bone sites do not react to treatment regimens in the same manner [ 27 ]. We measured levels of several serum biochemical markers to determine the influence of CQ on the state of bone turnover in these mice.

ALP that was measured is the total ALP which is an indirect marker for increased osteoblast activity, and with CQ treatment especially in the OVX group, there was increased activity which is in line with reports that show increased ALP activity in bone marrow cells in rats treated with CQ [ 18 ].

Osteogenic potential of cissus qudrangularis assessed with osteopontin expression

We also measured osteocalcin as a direct marker for bond activity and Trap5b as a marker for osteoclast ciswus. We observed that there were no statistical differences between the levels, of either of these markers in any of the groups studied; therefore, CQ does not alter the levels of these markers. Based on these results, we suggest that CQ does not change the bone turnover rate in these mice.


The mechanism s by which CQ inhibits bone loss is yet to be fully studied.

As a preliminary investigation, we measured a few proinflammatory cytokines. IL-6 is produced by osteoblasts and stimulate the formation cissuz osteoclasts [ 33 ]. Interestingly, IL-6 knockout mice do not lose cancellous bone after ovariectomy [ 33 ].

Our results clearly show quadrangularie CQ alters proinflammatory cytokines and maybe one of the major pathways used to reduce bone resorption—the characteristic response to ovariectomy. Based on the literature, CQ was also used to induce weight loss [ 634 ], but in our mice, we noticed that there was increased body weight and peritoneal fat. Both the quardangularis that reported weight reducing benefits of CQ were in obese humans.

The major difference between these reports and our study is that they were using already obese patients while the mice in our study were not obese to begin with. So, it may be that a stimulus obesity-linked proteins is required for CQ to reduce fat mass or the increase in fat mass is specific to mice and may not affect humans. We measured the levels of leptin, a hormone derived from the adipose tissue quacrangularis plays a key role in regulating energy intake and expenditure and also influences bone formation as well as bone resorption [ 35 ].

At lower than physiological concentrations leptin stimulates bone formation and probably can induce apoptosis of osteoclasts [ 36 ]. We were not surprised to find increased circulating levels of leptin and there was bone loss in the LC O mice, but CQ could protect bone in the long bones suggesting that CQ blocks the suadrangularis resorption action of leptin.

It will be interesting to see if CQ has any influence on the adipocytes found in the bone marrow. If CQ reduces the adipocytes in the bone marrow then the bone resorbing properties of leptin will be reduced as local leptin concentrations produced by increased adipocytes in the bone marrow will increase bone loss [ 37 ].

Therefore, leptin CQ interaction needs to be further studied to determine the mechanism by which CQ beneficially influences bone through leptin. CQ may primarily attenuate bone resorption in OVX mice through the downregulation of proinflammatory cytokines but it does not rule out the possibility that it may also act through other pathways.

There are reports that CQ also enhances bone mineralization by accumulating mucopolysaccharides at the site of bone formation [ 14 ]. Moreover, CQ is reported to increase calcium uptake and mechanical properties of bone in rats [ 15 ]. More investigations are necessary to elucidate the mechanism s by which CQ influences bone metabolism. We conclude that CQ can reduce OVX induced bone loss and it does this in the long bones in a site-specific manner with more effects on the cancellous bone of femur followed by tibia.

CQ probably reduces bone resorption primarily by downregulating proinflammatory cytokines that are often increased after ovariectomy. The beneficial effects of CQ are probably due to the flavanoids present. Although the mechanism s by which CQ attenuates ovariectomy-induced bone loss has to be studied, Quadrangulqris being an edible plant and with a history of medicinal effects, especially in healing bone fractures, may be a good supplement to existing medication for the reversal of postmenopausal bone cizsus.

Indexed in Web of Science. Subscribe to Table of Contents Alerts. Table of Contents Alerts. Abstract Women drastically loose bone during and after menopause leading to osteoporosis, a disease characterized by low bone mass increasing the risk of fractures with minor trauma. Introduction Osteoporosis is a disease associated with aging that causes fragility of bones making them susceptible to fractures with minor trauma.

Materials and Methods 2. Black bars represent distal femoral metaphysis; white bars represent femoral diaphysis. Cissus quadrangularis sham; CQ O: A Cortical thickness; B periosteal perimeter; C Endocortical perimeter. Black bars represent distal femoral metaphysis; White bars represent femoral diaphysis. Black bars represent proximal tibial metaphysis; white bars represent tibia fibula junction.

The figures are representative of the mean values that were obtained. View at Google Scholar U. View at Google Scholar L.