Stability and anti-proliferative properties of biologically active compounds extracted from Cistus L. after sterilization treatments

Abstract

The growing interest of oncologists in natural compounds such as polyphenols and flavonoids is encouraging the development of innovative and efficient carriers for the delivery of those drugs. This study examines carboxymethyl chitosan-based microcapsules created by spray drying as a method for delivering biologically active compounds isolated from the Cistus herb. Effects of sterilization and encapsulation on the polyphenol and flavonoid content of Cistus extract were investigated to optimize the production process. Furthermore, in vitro studies were carried out to examine the anticancer properties of sterilized polyphenols and flavonoids on glioblastoma cells isolated from oncological patients. Acquired results show high anticancer potential towards glioblastoma as well as low cytotoxicity towards non-cancer cell lines by the substances in question. Steam sterilization is shown to affect the content of biologically active compounds the least. We demonstrate that the investigated form of drug encapsulation is both efficient and potentially possible to scale up from the viewpoint of the pharmaceutical industry. According to apress statement launched by the International Agency for Research on Cancer from the World Health Organization (WHO), in 2018the global cancer burdenaffected 18.1 million new cases and 9.6 million of people passed away. Ten in 50 men and one in 60 women worldwide suffer from cancer during their life, and ten in 80 men and eleven in 110 women posse awaydue to thisillness. Moreover, cancer is a most frequent causeof children death. Worldwide, every year, approximately 300.000 of children are diagnosed by oncologists with a cancer disease 1,2. Furthermore, according to the published statistic data, the total number of people who are alive within 5 years of a cancer diagnosis, called the 5-year prevalence, is arround 43.8 million 3. As stated in the WHO report,the frequent types of cancer in men are cancer of lung, prostate, colorectal, stomach and liver, while in case on women, the most common type of cancer are: breast, colorectal, lung, cervix and thyroid cancer. The uncontrollable growth of tumor cells is the most fundamental aspect of cancer 4. Even if available therapies such as surgery, immunotherapy, chemotherapy, targeted therapy, hormone therapy and radiation therapy play a significant role in cancer treatment, drug resistance and toxicity remain main problems and challenges to cure cancer patients 5. Oncologists have called for basic investigationsand new upstream technologieswhich insustainably, efficiently and safely way will meet the current and future patients' needs 6,7. Additionally, during the last years the "integrative" oncology society has demanded advancesfrom scientists on the development of natural medicals 8,9. Indeed, the anticancer effects of biologically active compounds, such as natural polyphenols synthesized by fruits, vegetables, teas, apples, cocoa and other plants, have become a hot topic in many laboratories 10-12 .

UPLC-MS/MS Phytochemical Analysis of Two Croatian Cistus Species and Their Biological Activity

“…Since ancient times, Cistaceae have been used in ethnomedicine due to their pharmacological potential against a broad range of disorders, including various skin diseases, diarrhea, ulcers, dysentery, catarrh, menstruation difficulties, and gout due to a number of natural pharmacological compounds they consist of [ 2 , 3 , 4 ]. According to ethno-pharmacology, the Cistus species has been used due to its antimicrobial, antiproliferative, anticancer, antiviral, antioxidant, anti-inflammatory, antiulcerogenic, antidiarrheal, and antispasmodic activity [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. It is also known that some Cistus species have been used in human and animal diets, such as goats, lamb and beef [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ].…”

Current Perspectives of the Applications of Polyphenols and Flavonoids in Cancer Therapy

“…As observed in Figure 2 , there has been an exponential increase of research and publications related to the possible use of polyphenolic compounds in cancer therapy [ 15 ]. The fact that polyphenols can be extracted using simple and green techniques—such as ultrasound-assisted extraction, and that after being sterilized, polyphenols preserve most of their properties intact—will contribute to the study of these compounds as potential anticancer drugs [ 16 , 17 ].…”

Medical Plaster Enhancement by Coating with Cistus L. Extracts within a Chitosan Matrix: From Natural Complexity to Health Care Simplicity

“…They are widely contained in plants and can be classified into the following groups: phenolic acids, flavonoids, lignans, curcuminoids, stilbenes, and tannins [ 4 ]. Their pattern and substitution degrees determine a broad spectrum of biological properties such as free radical scavenging, metal-chelating, antimicrobial, immunostimulating, wound-healing and chemopreventive activities [ 5 , 6 , 7 , 8 , 9 ]. For instance, their natural antioxidant activity is able to inhibit oxidative chain reactions in human skin and can therefore prevent some skin diseases, premature ageing and skin damage, including wounds and burns [ 10 ].…”

“…They contain gallic acid, rutin, different flavonoid aglycones, and flavan-3-ols, as well as catechin, epicatechin, gallocatechin, gallocatechin-3-gallate and oligomeric procyanidin B1 and B3 as Biologically Active Compounds (BACs) [ 8 ]. In a previous paper, we showed that BAC content and activity are preserved when a steam sterilization process is employed, thus expanding the application opportunities in Medicine for these natural compounds [ 9 ].…”