**10. Conclusion**

differs greatly from other garlic-based preparations and may have considerable benefits in

On the whole, the results of our study demonstrate that long-term treatment with time-re‐ leased garlic-based drug Allicor provides a direct anti-atherosclerotic effect on carotid athe‐ rosclerosis. Being the remedy of natural origin, Allicor is safe with the respect to adverse effects and allows even perpetual administration, which may be quite necessary for preven‐ tion and treatment of subclinical atherosclerosis. These results encouraged clinical trials of two other drugs based on natural products, including: Inflaminat, possessing anti-cytokine activity and the phytoestrogen-rich drug Karinat, designed for postmenopausal women.

Atherosclerosis is regarded as a pathological process with elements of local aseptic inflam‐ mation, while inflammatory cytokines play a role at every stage of atherosclerosis develop‐ ment [104-107]. In this regard, drugs with systemic anti-inflammatory action may be effective for the prevention of atherosclerosis. In our study, we investigated the atheroscle‐ rosis regression effect of natural drug Inflaminat based on calendula, elder and violet. These plants are widely used in herbal medicine as anti-inflammatory agents. In a pilot study of Inflaminat using a protocol similar to the AMAR study Inflaminat demonstrated atheroscle‐ rosis regression effects and statistically significant difference from the baseline as well as from placebo group (Table 5). Thus, Inflaminat possesses atherosclerosis regression effect in

Number of participants 81 77 -

**Table 5.** Carotid IMT changes in 1-year Inflaminat pilot study\* significant differences, p<0.05, Wilcoxon's signed

ment therapy, but practically nothing is known on their effects on atherosclerosis.

Atherosclerosis prevention in postmenopausal women is a striking problem, since modern medicine does not provide any effective approach. Hormone replacement therapy was re‐ jected as a tool for atherosclerosis prevention in women due to the negative results of recent studies – WHI, PEPI and HERS [108-113]. So, the development of novel approaches is highly demanded. Phytoestrogens are often regarded as a possible alternative to hormone replace‐

We screened many natural phytoestrogen-rich components for their antiatherogenic activity using an ex vivo test system [39,61,114-117]. The most promising of these compounds were: garlic powder, extract of grape seeds, green tea leafs and hop cones - all produced a signifi‐ cant antiatherogenic effect. On the basis of their combination, the novel isoflavonoid-rich di‐ etary supplement Karinat was developed. It produces the most efficient antiatherogenic effect in cell culture models and is characterized by improved phytoestrogen profile, provid‐

ranked test;\*\*statistical significance of differences was estimated by Mann-Whitney U-test.


**Inflaminat Placebo р\*\***

42±75 (-9; 93) р=0,109

0.002

medicinal use.

204 Current Trends in Atherogenesis

asymptomatic men.

IMT, μm

This review illustrates the use of cultured human arterial cells for:


**Author details**

Veronika A. Myasoedova1

Development, Moscow, Russia

162(1), 206-211.

*sclerosis*, 86(2-3), 153-161.

*Communications*, 163(1), 489-494.

ces, Moscow, Russia

Australia

**References**

Alexander N. Orekhov1\*, Igor A. Sobenin2

\*Address all correspondence to: a.h.opexob@gmail.com

, Alexandra A. Melnichenko3

and Yuri V. Bobryshev4,1

1 Institute for Atherosclerosis Research, Skolkovo Innovative Center, Moscow, Russia

2 Russian Cardiology Research and Production Complex, Ministry of Healthcare and Social

3 Institute of General Pathology and Pathophysiology, Russian Academy of Medical Scien‐

4 Faculty of Medicine, School of Medical Sciences, University of New South Wales, Sydney,

[1] Martin, S. S., Blumenthal, R. S., & Miller, M. (2012). LDL cholesterol. the lower the

[2] Kruth, H. S. (2011). Receptor-independent fluid-phase pinocytosis mechanisms for induction of foam cell formation with native low-density lipoprotein particles. *Cur‐*

[3] Yuan, Y., Li, P., & Ye, J. (2012). Lipid homeostasis and the formation of macrophage-

[4] Orekhov, A. N., Tertov, V. V., Mukhin, D. N., & Mikhailenko, I. A. (1989). Modifica‐ tion of low density lipoprotein by desialylation causes lipid accumulation in cultured cells. Discovery of desialylated lipoprotein with altered cellular metabolism in the blood of atherosclerotic patients. *Biochemical and Biophysical Research Communications*,

[5] Orekhov, A. N., Tertov, V. V., & Mukhin, D. N. (1991). Desialylated low density lipo‐ protein- naturally occurring modified lipoprotein with atherogenic potency. *Athero‐*

[6] Tertov, V. V., Sobenin, I. A., Gabbasov, Z. A., Popov, E. G., & Orekhov, A. N. (1989). Lipoprotein aggregation as an essential condition of intracellular lipid accumulation caused by modified low density lipoproteins. *Biochemical and Biophysical Research*

[7] Tertov, V. V., Sobenin, I. A., Tonevitsky, A. G., Orekhov, A. N., & Smirnov, V. N. (1990). Isolation of atherogenic modified (desialylated) low density lipoprotein from

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,

http://dx.doi.org/10.5772/52967

207

Use of Natural Products for Direct Anti-Atherosclerotic Therapy



Cell cultures enable one to perform investigation on models: - in vitro (mass screening, study of the mechanism of drug action);



The in vitro and ex vivo models can be employed to reveal and investigate of:





Natural products can be considered as promising drugs for anti-atherosclerotic therapy. Two-year treatment with Allicor (garlic powder) has a direct anti-atherosclerotic effect on carotid atherosclerosis in asymptomatic men. Inflaminat (calendula, elder and violet), pos‐ sessing anti-cytokine activity, caused regression of carotid atherosclerosis as a result of 1 year treatment of asymptomatic men. Phytoestrogen-rich drug Karinat (garlic powder, extract of grape seeds, green tea leafs, hop cones, β-carotene, α-tocopherol and ascorbic acid) prevented development of carotid atherosclerosis in postmenopausal women.

Our basic studies have shown that cellular lipidosis is the principal event in genesis of athe‐ rosclerotic lesion. Using cellular models and natural products we have developed an ap‐ proach to prevent lipid accumulation in arterial cells. This led to regression of atherosclerosis and/or prevention of its progression in patients. So, our basic findings were successfully translated into clinical practice. As a result of this translation novel approach to anti-atherosclerotic therapy was developed. On the basis of our knowledge we developed drugs possessing direct anti-atherosclerotic activity. Our clinical trial confirmed the efficacy both novel approach and novel drugs.
