Review articles

By Mr. Abdalrahim Aisha , Prof. Khalid M. Abu-Salah , Prof. Zhari Ismail , Dr. Amin Malik Shah Abdul Majid
Corresponding Author Dr. Amin Malik Shah Abdul Majid
University of Science Malaysia, School of Pharmaceutical Sciences, Minden 11800, Pulau Pinang, Malaysia. - Malaysia 11800
Submitting Author Dr. Abdalrahim F Aisha
Other Authors Mr. Abdalrahim Aisha
University of Science Malaysia, School of Pharmaceutical Sciences, Minden 11800, Pulau Pinang - Malaysia 11800

Prof. Khalid M. Abu-Salah
King Saud University, Biochemistry Department and King Abdulla Institute for Nanotechnology, King Saud University, Riyadh 11451, Saudi Arabia - Saudi Arabia 11451

Prof. Zhari Ismail
University of Science Malaysia, School of Pharmaceutical Sciences, University Sains Malaysia (USM), Minden 11800, Pulau Pinang, Malaysia. - Malaysia 11800


Angiogenesis, Screening models, Rat aortic rings, Endothelial cells, Medicinal plants.

Aisha A, M. Abu-Salah K, Ismail Z, Abdul Majid A. Screening For Antiangiogenesis Activity In Natural Products: A Review. WebmedCentral PHARMACOLOGY 2010;1(12):WMC001315
doi: 10.9754/journal.wmc.2010.001315
Submitted on: 10 Dec 2010 03:23:01 PM GMT
Published on: 11 Dec 2010 02:15:29 PM GMT


Angiogenesis is a process of new blood vessel development that plays a vital role in embryonic development and numerous pathological conditions including cancer, rheumatoid arthritis, obesity, diabetic retinopathy, age related macular degeneration (AMD) and neurological disorders such as Parkinson and Alzheimer Disease. Recently a number of agents that inhibit angiogenesis have been approved to treat diseases such as cancer and AMD. The potential use of natural products to target angiogenesis is beginning to be appreciated especially their role in chemoprevention. This review will address some of the technical aspects in screening for antiangiogenic activity in natural products.


 Keywords: Angiogenesis, Screening models, Rat aortic rings, Endothelial cells, Medicinal plants.


Angiogenesis: definition and consequences

Angiogenesis, the formation of new blood vessels is a biological process that plays a fundamental role in embryonic development. In adults, angiogenesis plays an important role in some physiological situations such as in the female reproductive tract, in the placenta during pregnancy, and during wound healing (Auerbach et al., 2003; Folkman, 1995; Vailhe, Vittet & Feige, 2001). Pathological angiogenesis is unregulated process believed to play a key role in several pathological conditions including proliferative retinopathies, atherosclerosis, rheumatoid arthritis, psoriasis and tumor growth and metastasis (Creamer et al., 2002; Folkman, 1990; Folkman, 1995). Since tumor angiogenesis is essential for growth and metastasis of most solid malignancies (Folkman, 1990; Folkman, 1995) it has became a main target for developing novel cancer therapies (Eatock, Schatzlein & Kaye, 2000; Hurwitz et al., 2004; Pfeffer et al., 2003; Scappaticci, 2003). In this context this study was undertaken to investigate the antiangiogenic potential of herbal extracts aiming to develop new and effective anticancer therapies.


Angiogenesis: the sequence of events

To develop effective angiogenesis inhibitors, it is crucial to understand the mechanisms underlying the process. In tumor microenvironment, angiogenesis occurs as a consequence of angiogenic imbalance in which the proangiogenic factors predominate over antiangiogenic factors (Giordano & Johnson, 2001; Udagawa et al., 2002). The principal cells involved are endothelial cells, which form the lining of blood vessels and constitute almost the entirety of capillaries (Auerbach et al., 2003). Angiogenesis starts in response to stimulation by proangiogenic factors secreted by different types of cells including tumor cells, activated lymphocytes, or wound-associated macrophages causing activation of endothelial cells (Auerbach et al., 2003; Nicosia & Ottinetti, 1990; Risau, 1990). To form new blood vessels, the activated endothelial cells must first escape from their original location through the blood vessel’s basement membrane and its surrounding interstitial fluid, and then migrate towards the source of stimulus. Behind the migrating front, endothelial cells proliferate to provide the required number of cells that will reorganize to form three dimensional tubular structures. The final phase and the includes arrest of endothelial cells proliferation and stabilization of the immature capillary with pericytes and basement membrane (Auerbach et al., 2003; Benjamin, Hemo & Keshet, 1998; Bergers & Song, 2005; Vailhe, Vittet & Feige, 2001). Each step of this process can be a target for intervention by angiogenic modulators.


In vitro angiogenesis models 

The main practical challenge in angiogenesis studies is the selection of the right model. An ideal model would take into account all the representative steps of angiogenesis, from detachment of endothelial cells from the vascular wall to the final tubular morphogenesis, its maturation, and connection to a functional vascular network (Vailhe, Vittet & Feige, 2001). Furthermore, the model should be robust, rapid, reproducible, and easily quantifiable and it should allow assessment of multi-parameters including positive and negative controls (Staton, Reed & Brown, 2009; Vailhe, Vittet & Feige, 2001). Despite the availability of several in vitro models of angiogenesis, there still no standard model that can address all the steps occur in neovascularization. Therefore, a combination of different models is essential to cover the entire range of events during angiogenesis (Staton, Reed & Brown, 2009; Staton et al., 2004).


In vitro angiogenesis models include assays that utilize either cultured endothelial cells or tissue explants. Assays utilizing cultured endothelial cells include cell proliferation, migration, invasion and differentiation (Auerbach et al., 2003; Staton, Reed & Brown, 2009). These assays are robust, reproducible and applicable for high throughput screening (Arnaoutova & Kleinman, 2010; Liang, Park & Guan, 2007; Mosmann, 1983). However they have some drawbacks. In vitro assays involve the use of cultured endothelial cells which are propagated in a single culture. In addition the cells are in proliferation state which may interfere with the test compounds especially when targeting proangiogenic factors. On the contrary, in vivo angiogenesis process involves not only the quiescent endothelial cells, but involves interaction with other cell types including pericytes, smooth muscle cells, fibroblasts, macrophages and tumor cells.  In addition, endothelial cells are heterogenic since there are microvascular and macrovascular cells which differ in their morphology, physiology and response to angiogenesis modulating agents (Staton, Reed & Brown, 2009; Staton et al., 2004; Vailhe, Vittet & Feige, 2001). More important, passaging endothelial cells in vitro is associated with loss of their normal physiological properties, and resulting in variations in the results which may affect reproducibility of the model (Staton, Reed & Brown, 2009). Despite these limitations, the in vitro angiogenesis models that utilize endothelial cells still can be used but in combination with other in vivo or ex-vivo models in high throughput screening, and to get clues about the mechanism of action of pro- or anti-angiogenic agents by targeting particular events of angiogenesis (Auerbach et al., 2003). However care should be taken to select the right type of endothelial cells and to use cells at low passage number (Staton, Reed & Brown, 2009).

The other category of in vitro angiogenesis assays is based on the ability of activated endothelial cells to invade three dimensional substrate (Vailhe, Vittet & Feige, 2001), or the ability of tissue explants embedded within the substrate to form microvessels. Examples of tissue explants include rat or mouse aortic rings, porcine carotid artery, chick aortic arch, placental vein disk and fetal mouse bone explant (Nicosia & Ottinetti, 1990; Staton et al., 2004; Vailhe, Vittet & Feige, 2001). In this study we used a combination of the rat aortic rings as the primary screening model and endothelial cell proliferation in order to get the maximum benefits from these in vitro tests.


Rat aortic rings

The rat aortic rings model of angiogenesis was first developed by Nicosia and Ottinetti (Nicosia & Ottinetti, 1990). In this model, rat aortic rings are embedded in a matrix such as collagen, or fibrin gel and cultured in an optimized serum-free medium. A complex network of branching microvessels develops from endothelial cells of aortic intima in response to endogenous growth factors released from the dissected aortas (Nicosia et al., 1997). Quantification is can be achieved by measuring the number, length, or the area of microvessels outgrowth from the primary aortic explants (Brown et al., 1996; Nicosia et al., 1997).


The rat aortic rings is the most used angiogenesis model (Auerbach et al., 2003), and considered by many researchers to essentially simulate the in vivo angiogenesis environment since it involves the surrounding nonendothelial cells such as smooth muscle cells, pericytes and a supporting matrix (Bergers & Song, 2005; Hall, 2006; Howson et al., 2005; Nicosia & Villaschi, 1995). In addition, the endothelial cells are not altered by repeated passaging and are quiescent at the time of explantation and consequently are more representative of the situation found in vivo where angiogenesis is triggered and quiescent endothelial cells respond by becoming proliferative, migrating out from the existing vessels and differentiating into tubules (Staton, Reed & Brown, 2009; Staton et al., 2004). External growth factor supplements are not required since the required growth factors including VEGF are provided endogenously from the dissected aortas (Nicosia et al., 1997), and by a subset of immature immunocytes that can proliferate and differentiate into macrophages and ultimately stimulating angiogenesis (Zorzi et al., 2010). Other advantage of organ explant models of angiogenesis include the low cost, easy manipulation of treatment conditions, lack of inflammatory response seen with in vivo models and the possibility of generating many aortic rings from one animal (Kruger et al., 2001).


A major problem with all organ culture models of angiogenesis is the use of non-human tissues, which questions their applicability as preclinical screening assays since responses may be species specific (Staton, Reed & Brown, 2009). Even though, rat aortic model is a representative of almost all steps of angiogenesis except the blood flow, the model is not fully representative of the microvascular environment encountered in some diseases such as tumor microenvironment (Auerbach et al. 2000). Another drawback of these models arise during interpretation of results especially when looking for antiangiogenic agents since the inhibition of microvessels outgrowth may be due to nonselective cytotoxic activity rather than due to a ‘true’ antiangiogenic effect. Overall, the rat aortic model of angiogenesis is still the best in vitro model because it mimics the in vivo environment of angiogenesis in terms of initiation and the cascade of events; however other in vitro and in vivo models are needed to further support and confirm the results and to exclude species specific response.


Proliferation of endothelial cells model

Inhibition of the microvessels outgrowth from aortic rings may be due to nonselective cytotoxic effect induced by the test compounds or due to ‘true’ antiangiogenic activity. In order to discriminate the nonselective cytotoxic from antiangiogenic effects, extracts with more than 50% inhibition in rat aortic rings should be evaluated for cytotoxicity on human umbilical vein endothelial cells (HUVECs) and other human cell lines. The main interest is to find extracts with significant inhibition of the microvessels outgrowth in rat aortic rings, without cytotoxic effect on HUVECs, or the extracts should be selective cytotoxic towards HUVECs. Besides distinguishing extracts with antiangiogenic activity from those with nonselective cytotoxicity, the combination of these two models can help to get insights into the mechanism of action of extracts with interesting activity. 


Medicinal plants as a source of antiangiogenic agents

Medicinal plants continue to provide new and important leads against different pharmacological targets including cancer, AIDS, Alzheimer’s disease, malaria, and pain (Balunas & Kinghorn, 2005). Inhibition of angiogenesis which was suggested by Folkman on 1971 is now considered to be one of the most promising strategies leading to the development of new antineoplastic therapies (Folkman, 1971). Accordingly, numerous bioactive plant-derived compounds have been tested for their antiangiogenic potential. Among the most frequently studied are polyphenols present in fruits and vegetables (Cao, Cao & Brakenhielm, 2002; Mojzis et al., 2008). There are close to 5000 different polyphenols described so far which are divided into subgroups including  isoflavones, flavonoids and lignans (Cao, Cao & Brakenhielm, 2002). Recently, several polyphenols isolated from various plants have been found to be potent inhibitors of angiogenesis for example catechins from green tea (Leong, Mathur & Greene, 2009), resveratrol from grapes and other sources (Cao et al., 2005), quercetin (Tan et al., 2003), rosmarinic acid (Huang & Zheng, 2006), genistein (Su et al., 2005), curcumin (Arbiser et al., 1998) and several other compounds. Other compounds were also reported with interesting antiangiogenic activity including the triterpenes such as ursolic acid (Kanjoormana & Kuttan, 2010), oleanolic acid (Sogno et al., 2009), lupeol (You et al., 2003) and betulinic acid (Mukherjee et al., 2004). Polyphenols and triterpenes are among the most abundant secondary metabolites in higher plants (Jager et al., 2009; Mojzis et al., 2008), therefore medicinal plants can provide high potentiality for discovery of new and effective antiangiogenic agents. 

Criteria for plants selection 

Generally plants those are rich in polyphenols, triterpenes with strong antioxidant and anti-inflammatory effects tend to have antiangiogenic activity. Polyphenols and triterpenes have a wide range of pharmacological activities including antioxidant, anti-inflammatory, cardioprotective, and anticancer (Liu, 1995; Mojzis et al., 2008). Other compounds that have anti-inflammatory and antioxidant activity with good antiangiogenic activity includes betulinic acid, green tea catechins, vitamin E and resveratrol (Cao, Cao & Brakenhielm, 2002; Huang & Zheng, 2006; Mojzis et al., 2008; Mukherjee et al., 2004; Tan et al., 2003). Amongst the many plants with good antiangiogenic activity include Punica granatum L (Toi et al., 2003). Garcinia mangostana L which have been shown to have strong antioxidant and anti-inflammatory effects could good source of new and effective antiangiogenic agents (Chen, Yang & Wang, 2008; Moongkarndi et al., 2004). Rasadah and his colleagues wrote on the anti-inflammatory activity of Sandoricum koetjape Merr  (Rasadah et al., 2004). Anti-inflammatory activity of Syzygium species from the family Myrtaceae has also been reported (Muruganandan et al., 2001). Delonix regia was found to be rich in carotinoids with a well known antioxidant activity (Jungalwala & Cama, 1962). Extracts from Cassia fistula Linn were reported to have both antioxidant and anti-inflammatory effects (Ilavarasana, Mallikab & Venkataramanc, 2005).


All in all, many natural products tend to have high level of antioxidant property, a key feature that is useful in angiogenesis inhibition. It is thus not surprising to find many of them can potentially prevent cancer growth and development given the vital role of angiogenesis in cancer. It is however, important to utilize effective screening methods that can detect anti-angiogenic activity via the various routes and pathways. Without such methods, potential lead compounds may be missed.


1. Aisha, A.F.A., Abu-Salah, K.M., Darwis, Y. and Abdul Majid, A.M.S., 2009. Screening of Antiangiogenic Activity of Some Tropical Plants by Rat Aorta Ring Assay Int. J. Pharamcol., 5(6), 370-376.
2.Arnaoutova, I. and Kleinman, H.K., 2010. In vitro angiogenesis: endothelial cell tube formation on gelled basement membrane extract. Nat Protoc, 5(4), 628-35. uids=20224563
3.Auerbach, R., Lewis, R., Shinners, B., Kubai, L. and Akhtar, N., 2003. Angiogenesis assays: a critical overview. Clin Chem, 49(1), 32-40. uids=12507958
4.Balunas, M.J. and Kinghorn, A.D., 2005. Drug discovery from medicinal plants. Life Sci, 78(5), 431-41. uids=16198377
5.Bergers, G. and Song, S., 2005. The role of pericytes in blood-vessel formation and maintenance. Neuro Oncol, 7(4), 452-64. uids=16212810
6.Brown, K.J., Maynes, S.F., Bezos, A., Maguire, D.J., Ford, M.D. and Parish, C.R., 1996. A novel in vitro assay for human angiogenesis. Lab Invest, 75(4), 539-55. uids=8874385
7.Cao, Y., Cao, R. and Brakenhielm, E., 2002. Antiangiogenic mechanisms of diet-derived polyphenols. J Nutr Biochem, 13(7), 380-390. uids=12121824
8.Cao, Y., Fu, Z.D., Wang, F., Liu, H.Y. and Han, R., 2005. Anti-angiogenic activity of resveratrol, a natural compound from medicinal plants. J Asian Nat Prod Res, 7(3), 205-13. uids=15621628
9.Folkman, J., 1971. Tumor angiogenesis: therapeutic implications. N Engl J Med, 285(21), 1182-6. uids=4938153
10.Folkman, J., 1990. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst, 82(1), 4-6. uids=1688381
11.Folkman, J., 1995. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med, 1(1), 27-31. uids=7584949
12.Hall, A.P., 2006. Review of the pericyte during angiogenesis and its role in cancer and diabetic retinopathy. Toxicol Pathol, 34(6), 763-75. uids=17162534
13.Howson, K.M., Aplin, A.C., Gelati, M., Alessandri, G., Parati, E.A. and Nicosia, R.F., 2005. The postnatal rat aorta contains pericyte progenitor cells that form spheroidal colonies in suspension culture. Am J Physiol Cell Physiol, 289(6), C1396-407. uids=16079185
14.Huang, S.S. and Zheng, R.L., 2006. Rosmarinic acid inhibits angiogenesis and its mechanism of action in vitro. Cancer Lett, 239(2), 271-80. uids=16239062
15.Ilavarasana, R., Mallikab, M. and Venkataramanc, S., 2005. Anti-inflammatory and Antioxidant Activities of Cassia Fistula LINN Bark Extracts. Afr. J. Trad. CAM, 2(1), 70-85.
16.Jager, S., Trojan, H., Kopp, T., Laszczyk, M.N. and Scheffler, A., 2009. Pentacyclic triterpene distribution in various plants - rich sources for a new group of multi-potent plant extracts. Molecules, 14(6), 2016-31. uids=19513002
17.Jungalwala, F.B. and Cama, H.R., 1962. Carotenoids in Delonix regia (Gul Mohr) Flower. Biochem. J. , 85(1), 1-8.
18.Kruger, E.A., Duray, P.H., Price, D.K., Pluda, J.M. and Figg, W.D., 2001. Approaches to preclinical screening of antiangiogenic agents. Semin Oncol, 28(6), 570-6. uids=11740811
19.Lee, E.Y., Chung, C.H., Kim, J.H., Joung, H.J. and Hong, S.Y., 2006. Antioxidants ameliorate the expression of vascular endothelial growth factor mediated by protein kinase C in diabetic podocytes. Nephrol Dial Transplant, 21(6), 1496-503. uids=16484238
20.Liang, C.C., Park, A.Y. and Guan, J.L., 2007. In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc, 2(2), 329-33. uids=17406593
21.Mojzis, J., Varinska, L., Mojzisova, G., Kostova, I. and Mirossay, L., 2008. Antiangiogenic effects of flavonoids and chalcones. Pharmacol Res, 57(4), 259-65. uids=18387817
22.Mosmann, T., 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods, 65(1-2), 55-63. uids=6606682
23.Mu, P., Gao, X., Jia, Z.J. and Zheng, R.L., 2008. Natural antioxidant pedicularioside G inhibits angiogenesis and tumourigenesis in vitro and in vivo. Basic Clin Pharmacol Toxicol, 102(1), 30-4. uids=17973903
24.Mukherjee, R., Jaggi, M., Rajendran, P., Siddiqui, M.J.A., Srivastava, S.K., Vardhan, A. and Burman, A.C., 2004. Betulinic acid and its derivatives as anti-angiogenic agents. Bioorganic & Medicinal Chemistry Letters, 14(9), 2181-2184.
25.Nicosia, R.F., Lin, Y.J., Hazelton, D. and Qian, X., 1997. Endogenous regulation of angiogenesis in the rat aorta model. Role of vascular endothelial growth factor. Am J Pathol, 151(5), 1379-86. uids=9358764
26.Nicosia, R.F. and Ottinetti, A., 1990. Growth of microvessels in serum-free matrix culture of rat aorta. A quantitative assay of angiogenesis in vitro. Lab Invest, 63(1), 115-22. uids=1695694
27.Nicosia, R.F. and Villaschi, S., 1995. Rat aortic smooth muscle cells become pericytes during angiogenesis in vitro. Lab Invest, 73(5), 658-66. uids=7474939
28.Rasadah, M.A., Khozirah, S., Aznie, A.A. and Nik, M.M., 2004. Anti-inflammatory agents from Sandoricum koetjape Merr. Phytomedicine, 11(2-3), 261-3. uids=15070182
29.Sogno, I., Vannini, N., Lorusso, G., Cammarota, R., Noonan, D.M., Generoso, L., Sporn, M.B. and Albini, A., 2009. Anti-angiogenic activity of a novel class of chemopreventive compounds: oleanic acid terpenoids. Recent Results Cancer Res, 181(209-12. uids=19213570
30.Staton, C.A., Reed, M.W. and Brown, N.J., 2009. A critical analysis of current in vitro and in vivo angiogenesis assays. Int J Exp Pathol, 90(3), 195-221. uids=19563606
31.Staton, C.A., Stribbling, S.M., Tazzyman, S., Hughes, R., Brown, N.J. and Lewis, C.E., 2004. Current methods for assaying angiogenesis in vitro and in vivo. Int J Exp Pathol, 85(5), 233-48. uids=15379956
32.Su, S.J., Yeh, T.M., Chuang, W.J., Ho, C.L., Chang, K.L., Cheng, H.L., Liu, H.S., Hsu, P.Y. and Chow, N.H., 2005. The novel targets for anti-angiogenesis of genistein on human cancer cells. Biochem Pharmacol, 69(2), 307-18. uids=15627483
33.Tan, W.F., Lin, L.P., Li, M.H., Zhang, Y.X., Tong, Y.G., Xiao, D. and Ding, J., 2003. Quercetin, a dietary-derived flavonoid, possesses antiangiogenic potential. Eur J Pharmacol, 459(2-3), 255-62. uids=12524154
34.Toi, M., Bando, H., Ramachandran, C., Melnick, S.J., Imai, A., Fife, R.S., Carr, R.E., Oikawa, T. and Lansky, E.P., 2003. Preliminary studies on the anti-angiogenic potential of pomegranate fractions in vitro and in vivo. Angiogenesis, 6(2), 121-8. uids=14739618
35.Vailhe, B., Vittet, D. and Feige, J.J., 2001. In vitro models of vasculogenesis and angiogenesis. Lab Invest, 81(4), 439-52. uids=11304563
36.You, Y.J., Nam, N.H., Kim, Y., Bae, K.H. and Ahn, B.Z., 2003. Antiangiogenic activity of lupeol from Bombax ceiba. Phytother Res, 17(4), 341-4. uids=12722136
37.Zorzi, P., Aplin, A.C., Smith, K.D. and Nicosia, R.F., 2010. Technical Advance: The rat aorta contains resident mononuclear phagocytes with proliferative capacity and proangiogenic properties. J Leukoc Biol, 88(5), 1051-9. uids=20628067

Source(s) of Funding

University of Science Malaysia

Competing Interests

No competing interests exist


This article has been downloaded from WebmedCentral. With our unique author driven post publication peer review, contents posted on this web portal do not undergo any prepublication peer or editorial review. It is completely the responsibility of the authors to ensure not only scientific and ethical standards of the manuscript but also its grammatical accuracy. Authors must ensure that they obtain all the necessary permissions before submitting any information that requires obtaining a consent or approval from a third party. Authors should also ensure not to submit any information which they do not have the copyright of or of which they have transferred the copyrights to a third party.
Contents on WebmedCentral are purely for biomedical researchers and scientists. They are not meant to cater to the needs of an individual patient. The web portal or any content(s) therein is neither designed to support, nor replace, the relationship that exists between a patient/site visitor and his/her physician. Your use of the WebmedCentral site and its contents is entirely at your own risk. We do not take any responsibility for any harm that you may suffer or inflict on a third person by following the contents of this website.

2 reviews posted so far

Antiangiogenesis Activity
Posted by Mr. Suchir Arora on 12 Dec 2010 11:42:35 AM GMT

0 comments posted so far

Please use this functionality to flag objectionable, inappropriate, inaccurate, and offensive content to WebmedCentral Team and the authors.


Author Comments
0 comments posted so far


What is article Popularity?

Article popularity is calculated by considering the scores: age of the article
Popularity = (P - 1) / (T + 2)^1.5
P : points is the sum of individual scores, which includes article Views, Downloads, Reviews, Comments and their weightage

Scores   Weightage
Views Points X 1
Download Points X 2
Comment Points X 5
Review Points X 10
Points= sum(Views Points + Download Points + Comment Points + Review Points)
T : time since submission in hours.
P is subtracted by 1 to negate submitter's vote.
Age factor is (time since submission in hours plus two) to the power of 1.5.factor.

How Article Quality Works?

For each article Authors/Readers, Reviewers and WMC Editors can review/rate the articles. These ratings are used to determine Feedback Scores.

In most cases, article receive ratings in the range of 0 to 10. We calculate average of all the ratings and consider it as article quality.

Quality=Average(Authors/Readers Ratings + Reviewers Ratings + WMC Editor Ratings)