Quality Control of Herbal Medicines: From Traditional Techniques to State-of-the-art Approaches.

Herbal medicines are important options for the treatment of several illnesses. Although their therapeutic applicability has been demonstrated throughout history, several concerns about their safety and efficacy are raised regularly. Quality control of articles of botanical origin, including plant materials, plant extracts, and herbal medicines, remains a challenge. Traditionally, qualitative (e.g., identification and chromatographic profile) and quantitative (e.g., content analyses) markers are applied for this purpose. The compound-oriented approach may stand alone in some cases (e.g., atropine in Atropa belladonna). However, for most plant materials, plant extracts, and herbal medicines, it is not possible to assure quality based only on the content or presence/absence of one (sometimes randomly selected) compound. In this sense, pattern-oriented approaches have been extensively studied, introducing the use of multivariate data analysis on chromatographic/spectroscopic fingerprints. The use of genetic methods for plant material/plant extract authentication has also been proposed. In this study, traditional approaches are reviewed, although the focus is on the applicability of fingerprints for quality control, highlighting the most used approaches, as well as demonstrating their usefulness. The literature review shows that a pattern-oriented approach may be successfully applied to the quality assessment of articles of botanical origin, while also providing directions for a compound-oriented approach and a rational marker selection. These observations indicate that it may be worth considering to include fingerprints and their data analysis in the regulatory framework for herbal medicines concerning quality control since this is the foundation of the holistic view that these complex products demand.

Cytotoxicity and Antiviral Activities of Haplophyllum tuberculatum Essential Oils, Pure Compounds, and Their Combinations against Coxsackievirus B3 and B4.

Haplophyllum tuberculatum is a plant commonly used in folk medicine to treat several diseases including vomiting, nausea, infections, rheumatism, and gastric pains. In the current study, H. tuberculatum essential oils, hydrosols, the pure compounds R-(+)-limonene, S-(-)-limonene, and 1-octanol, as well as their combinations R-(+)-limonene/1-octanol and S-(-)-limonene/1-octanol, were screened for their cytotoxicity on HEp-2 cells after 24, 48, and 72 h, and then tested for their activity against Coxsackievirus B3 and B4 (CV-B3 and CV-B4) at 3 different moments: addition of the plant compounds before, after, or together with virus inoculation. Results showed that the samples were more cytotoxic after 72 h than after 24 h or 48 h cell contact. However, the combinations R-(+)-limonene/1-octanol and S-(-)-limonene/1-octanol showed less effect on HEp-2 cells than pure R-(+)-limonene and S-(-)-limonene after 24 h, 48 h, and 72 h. 1-octanol exhibited the highest concentration causing 50% cytotoxicity (CC50) on HEp-2 cells after 24 h (CC50 = 93 µg/mL) and 48 h (CC50 = 83 µg/mL). The antiviral assays showed that the tested samples exhibited potent inhibition of CV-B. IC50 values ranged from 0.66 µg/mL to 28.4 µg/mL. In addition, CV-B3 was more sensitive than CV-B4. Both CV-B strains are more inhibited when cells were pretreated with the plant compounds. The hydrosols have no effect, neither on HEp-2 cells nor on the virus. 1-octanol, S-(-), and R-(+)-limonene/1-octanol had important selectivity indexes over time. Although essential oils had potent antiviral activity, they can be considered for application in the pretreatment of cells. However, 1-octanol and the combinations are within the safety limits, and thus, they can be used as an active natural antiviral agent for CV-B3 and CV-B4 inhibition.

Four Pistacia atlantica subspecies (atlantica, cabulica, kurdica and mutica): A review of their botany, ethnobotany, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Pistacia atlantica (wild pistachio) belongs to the Anacardiaceae family, and growing from the Mediterranean basin to central Asia, especially in Iran, Turkey, Iraq and Saudi Arabia where it is extensively used in traditional medicine for a wide range of ailments related to relieving upper abdominal discomfort and pain, dyspepsia and peptic ulcer. OBJECTIVE: Despite the diverse biological activities of P. atlantica, there is no current review summarizing medicinal properties of its subspecies, including cabulica, kurdica and mutica. Thus, this paper aims to explore the current understanding of the chemical, pharmacological, and biochemical properties of the extracts and the main active constituents found in each subspecies of this plant. METHODS: Peer-reviewed articles, using "Pistacia atlantica" as search term (″all fields″), were retrieved from Scifinder, Pubmed, Science direct, Wiley, Springer, ACS, Scielo, Web of Science and other web search instruments (Google Scholar, Yahoo search). Papers published until July 2020 are considered. In addition, various books were consulted that contained botanical and ethnopharmacological information. The information provided in this review is based on peer-reviewed papers in English and French. RESULTS: Phytochemical studies have shown the presence of numerous valuable compounds, including volatile compounds, flavonoids, phenolic compounds, fatty acids, tocopherols and phytosterols. P. atlantica contains also minerals and trace elements, like iron, lead, copper, potassium, sodium and calcium; fatty acids, like oleic, linoleic, and palmitic acid; fat-soluble vitamins, such as α, ß, γ and δ tocopherols; phytosterols, like betasitosterol, stigmasterol, campesterol and Δ5-avenasterol. Crude extracts and isolated compounds from P. atlantica show a wide range of pharmacological properties, such as antimicrobial, antifungal, anti-inflammatory, analgesic, antinociceptive, wound healing, anticancer, cytotoxic, anticholinesterase, antidiabetic, hepatoprotective, urease inhibition, antihypertension, nipple fissure healing, antileishmanial and antiplasmodial activities. However, there are no reports summarizing the P. atlantica bioactivity, its therapeutic value, and the roles played by each of the numerous phytoconstituents. CONCLUSION: Many traditional uses of P. atlantica and its subspecies have now been confirmed by pharmacologic research. Systematic phytochemical investigation of the P. atlantica subspecies and the pharmacological properties, especially the mechanisms of action and toxicology, to illustrate their ethnomedicinal use, to explore the therapeutic potential and support further health-care product development, will undoubtedly be the focus of further research. Therefore, detailed and extensive studies and clinical evaluation of P. atlantica subspecies should be carried out in future for the safety approval of therapeutic applications.

Selected-ion flow-tube mass-spectrometry (SIFT-MS) fingerprinting versus chemical profiling for geographic traceability of Moroccan Argan oils.

This study investigated the effectiveness of SIFT-MS versus chemical profiling, both coupled to multivariate data analysis, to classify 95 Extra Virgin Argan Oils (EVAO), originating from five Moroccan Argan forest locations. The full scan option of SIFT-MS, is suitable to indicate the geographic origin of EVAO based on the fingerprints obtained using the three chemical ionization precursors (H3O+, NO+ and O2+). The chemical profiling (including acidity, peroxide value, spectrophotometric indices, fatty acids, tocopherols- and sterols composition) was also used for classification. Partial least squares discriminant analysis (PLS-DA), soft independent modeling of class analogy (SIMCA), K-nearest neighbors (KNN), and support vector machines (SVM), were compared. The SIFT-MS data were therefore fed to variable-selection methods to find potential biomarkers for classification. The classification models based either on chemical profiling or SIFT-MS data were able to classify the samples with high accuracy. SIFT-MS was found to be advantageous for rapid geographic classification.

Potentially antidiabetic and antihypertensive compounds identified from Pistacia atlantica leaf extracts by LC fingerprinting.

The objective of this paper is to evaluate the variations in the ability of Pistacia atlantica leaves to inhibit enzymes linked to type 2 diabetes (α-amylase and α-glucosidase) and to hypertension (angiotensin converting enzyme-I (ACE-I)), depending on harvesting month, gender and growing region, as well as to identify the peaks in chromatographic fingerprints that potentially correspond to components with enzymatic inhibitory activities. In this study, LC fingerprints of P. atlantica leave extracts were developed. Peaks which were probably responsible for the anti-amylase, anti-glucosidase and anti-ACE-I activities were assigned. For the latter purpose, the relevant information was extracted, linking the chromatographic fingerprints with the activities using a linear multivariate calibration technique, i.e., Partial Least Squares (PLS) regression. Prior to the construction of the models, the fingerprints are aligned using a warping method, called Correlation Optimized Warping (COW). Besides COW, different other data pretreatment methods were applied and compared. Our findings revealed that the influence of the growing region and gender on the α-amylase, α-glucosidase and ACE-I inhibitory activities of P. atlantica leaves was less important than the harvest time. Thirteen common peaks were selected from the chromatograms and used as a dataset to model the biological activities. The peaks potentially responsible for the biological activity of the samples were indicated by studying the regression coefficients of the models. Seven peaks corresponding to possibly anti-amylase compounds were found, while 6 peaks were considered important for inhibiting the α-glucosidase activity. Furthermore, the regression coefficients of the hypertension model indicated eight peaks as being important for inhibiting the ACE-I activity. The contributions of individual phenolic compounds of P. atlantica leaves to the α-amylase, α-glucosidase and ACE-I inhibitory activities were also identified. This investigation showed that the extract of P. atlantica leaves provides a rational basis for the isolation and development of antidiabetic and antihypertensive agents.

Seasonal, gender and regional variations in total phenolic, flavonoid, and condensed tannins contents and in antioxidant properties from Pistacia atlantica ssp. leaves.

CONTEXT: The widespread use of Pistacia atlantica Desf. ssp. (Anacardiaceae) in traditional medicine can be partly attributed to the content of its secondary metabolites, in particular, the phenolic compounds. OBJECTIVE: The effects of harvest period, growing region and gender on the phenolic compounds, flavonoids and condensed tannins contents were studied, as well as on the antioxidant activities of P. atlantica leaves in order to provide a scientific basis for optimal collection. MATERIALS AND METHODS: Leaves were collected monthly from April to October 2010 in two Algerian sites. The powdered leaves were used for preparing the ethyl acetate extract. Contents of total phenolics (TPC), flavonoids (FC) and condensed tannins (CTC) were determined spectrophotometrically. Antioxidant activity was evaluated through radical scavenging activity (RSA) of 2,2-diphenyl-1-picrylhydrazyl (250 µM) and the reducing power capacity (RPC) determination by K3Fe(CN)6 (1%). RESULTS: The TPC was found to vary from 79 ± 13 to 259 ± 8 mg gallic acid equivalents/g of dry weight (DW) during the study period. The RSA and RPC varied between 262 ± 18 and 675 ± 21 mg Ascorbic Acid Equivalent (AAE)/g DW, and from 259 ± 16 to 983 ± 20 mg AAE/g DW, respectively. A seasonal pattern was observed consisting of a decrease in TPC content and RPC from spring to autumn. The FC, CTC and RSA did not show a seasonal pattern. DISCUSSION AND CONCLUSION: Our findings showed that secondary metabolite content and antioxidant activities of P. atlantica leaves were more influenced by harvest time and growing region than by gender.