Frontiers in Natural Product Chemistry

 Extracts obtained from many plants have recently gained popularity and scientific interest for their antibacterial, antifungal and antioxidant activity. Many results have been reported on the antimicrobial properties of plant extracts containing essential oils and different classes of phenolic compounds. In this chapter, we will discuss the traditional usage and the biological and pharmacological properties of various Cistus species, with particular emphasis on Cistus species growing in Sardinia. Cistaceae family is widespread in the Mediterranean region with several species, and it is known as a traditional natural remedy. Cistus genus grows in Sardinia with populations of C.monspeliensis, C.salvifolius, C. albidus and C. creticus subspecies: C.creticus subsp. creticus, C.creticus subsp. corsicus, and C.creticus subsp. eriocephalus. Despite being widespread, only a few phytochemical research has been reported for Cistus species growing in Sardinia. Moreover, C.creticus subsp. eriocephalus (Viv) Greuter & Burdet growing in Sardinia is characterized by an important polymorphism due to hybridization and occurrence of various ecotypes based on intermediate morphological characters. The recent studies have shown that the extracts of Cistus species may be used as therapeutic agents in a wide range of human diseases. The use of plant extracts for controlling postharvest fungal pathogens can enhance healthy fruit production. Further knowledge regarding the bioactivity of Sardinian Cistus species will be useful to verify their potential as profitable sources of functional ingredients in applications, such as food preservation, cosmetic, hygiene or medical device

Phytohormone abscisic acid (ABA) regulates the growth and development of plants as well as their response to environmental changes. Recently, the regulations of ABA during fruit ripening and stress resistance were discovered in two types of fruits (climacteric and non-climacteric fruits). However, it is challenging to understand the physiological, biochemical, and molecular biological mechanisms in fruit ripening and stress response controlled by ABA. ABA is involved in fruit development processes, including young fruit growth, fruit ripening onset, ripening process and quality formation. Meanwhile, ABA plays an important role in fruit adapting to environmental stresses. ABA works through the adjustment of its concentration and signal transduction. This review summarizes the current knowledge regarding ABA in the regulation of fruit development and ripening as well as in responses to environmental stresses. 

Biflavonoids are dimers of monomeric flavonoids and have reported to exhibit several pharmacological activities, like anti-microbial, anti-inflammatory, antienzymatic, antioxidant, anticancer, anti-Perkinson, anti-ulcer, anti-hypertensive, antidiabetic, anti-depressant and anti-protozoan. Extensive research work on this important segment of natural compounds is in progress. In this chapter, we report the progress of research on natural biflavonoids from the period of 2005 to early 2020; it includes enlisting newly isolated bioflavonoids from plant sources, biological activities exhibited by the known as well as new compounds and synthetic strategies developed for synthesizing such compounds. In this time period, a total of 247 biflavonoids have been reported either in terms of their first-time appearance or evaluation of their biological activities or both. Out of the reported 247 biflavonoids, 176 have been reported as new compounds from natural plant sources. They have been reported to exhibit a wide range of biological and pharmacological properties, including antimicrobial and antiviral, cytotoxic and anti-cancer, anti-diabetic, anti-anoxic, antioxidant, NO-inhibitory activity, anti-enzymatic, anti-HIV, anti thrombin, antiallergic, cytoprotective, neuroprotective and anti-inflammatory, which have been discussed in a comprehensive manner. Different synthetic strategies that have been reported for the synthesis of structurally different biflavonoids are also included. This chapter cites 177 references. 

The human body is exposed to natural sources of ionizing radiation including cosmic rays, radionuclides disposed on the Earth's crust, air, water, and food. In addition, man-made radiation sources for military and civil purposes such as the use of radiation in health care, medical procedures in the diagnosis and treatment of diseases, scientific researches, and energy production can contribute to the increased exposure and may affect the human cells. Many derivatives of plant extracts or genetically modified plants have been employed as radiomodifiers as they are compounds that can modify the biological response to the damage induced by the radiation. On the other hand, radiomodulators can be used for varied medical applications such as radioprotection and radiosensitization of tumor cells. This chapter aims to identify, analyze, and synthesize results of independent studies through an integrative review, which evaluated the protective effects of plant metabolites on cell injury caused by radiation therapy against cancer and high doses of radiation exposure. 

Colorimetric or spectrophotometric methods have been used over the past few decades for rapid and convenient estimation of certain classes of flavonoids in fruits, vegetables, grains, raw herbal material, herbal formulations, and nutraceuticals. This has resulted in a surge in the numbers of research articles discussing the use of these methods for comparison between numbers of samples of the same kind, such as analysis to find differences between various tea samples, food articles, raw drug powders, etc. However, these methods are not selective since several factors influence color development. Also, the reagents used to form the colored complex are not specific to a certain class of compounds. There are studies performed where all compounds belonging to a particular class do not react uniformly to the reagents used in the method. Chelation using AlCl3 was used to develop deep yellow-colored complexes of the flavonoids and absorbance was subsequently measured at 420 nm, using quercetin as the standard. In a modification, potassium acetate was added after the addition of AlCl3 , and the absorbance was measured at 415 nm, again against standard quercetin solutions, wherein only flavones and flavonols were estimated. A study conducted by our team proves that all flavonoids do not form complexes that absorb at 420 nm, and each flavonoid shows variation in absorption maxima. Only flavonoids with o-dihydroxy systems show good results, while others absorb at either higher or lower wavelengths. This research work has been one of the top 20 most downloaded articles in flavonoid chemistry since its date of publication. Catechins, flavanones, and anthocyanins cannot be estimated using this method, due to either inability to bind with AlCl3 in an appropriate manner or due to differences in absorption maxima of the complex formed. Flavanones like naringenin, naringin, and hesperidin have been estimated using the 2,4-dinitrophenyl hydrazine method. The method does not work for flavonols and flavones. Estimation of catechins in tea samples has been described where caffeine is removed from solution using extraction by chloroform, and the absorbance of the aqueous phase is taken at 274 nm. The technique however is flawed since the aqueous extract will also contain phenolic acids like gallic, protocatechuic, and syringic acids, and a good amount of flavonols such as quercetin and kaempferol, which also absorb around 274 nm. These phenolic acids and flavonols need to be removed before the estimation of catechins. The reaction of flavanols like catechin and epicatechin with vanillin in presence of H2SO4 yields redcolored complexes that show absorptions around 500 nm, but certain matrices interferences of proanthocyanins. Many flavonoid compounds occur in the form of glycosides, where the presence of sugar molecules like glucose, rhamnose, galactose, etc. can hamper complex formation responsible for color development. The effect of hydrolysis can yield better results to remove the sugar moieties, and the aglycones can be estimated. Another widely used method is the Folin-Ciocalteu method for estimation of phenolics, developed by Folin and Denis in 1915, and modified by Singleton and Rossi in 1965, where a blue-colored complex due to reduction of molybdenum by phenolate ions formed in a basic medium. One major drawback of this method is that the absorption maxima of the complex formed varies between 620 and 765 nm. Studies also confirm that this assay is not specific to only phenolics, but can also react to interferences of ascorbic acid, reducing sugars, certain metals, amino acids, and reducing agents like NaHSO3 . Most results published in thousands of research papers worldwide are erroneous due to a lack of knowledge of the actual chemical reactions taking place in the estimation methods, and how the flavonoids react with the reagents.