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.

Psidium L. genus: A review on its chemical characterization, preclinical and clinical studies.

The Myrtaceae family is considered one of the largest known botanical families and the genus Psidium is among the most economically interesting. Psidium genus comprises approximately 112 species, and it has been extensively studied, mainly because of Psidium guavaja species. Phytochemical investigations confirmed the presence of phenolics as the main compounds, as well as the essential oils, which were also widely investigated. Pharmacological studies report analgesic, anthelminthic, acaricidal, antihiperglicemic, among other biological activities for different species. The present review covers the relevant literature until 2019 and outlines the current data on chemical composition, preclinical and clinical studies on Psidium species, as well as the main possible mechanisms of action responsible for the described activities. Therefore, it can provide a reference for pharmaceutical research and clinical application of this genus.

An ultrasound assisted extraction-solid-phase extraction-ultra-performance liquid chromatography combined strategy for atropine determination in Atropa belladonna leaves.

Atropine is an antimuscarinic alkaloid identified in Atropa belladonna. In pharmacopeias, percolation is standardized as an extraction method for A. belladonna leaves, along with liquid-liquid extraction as a cleanup procedure and titration as an analytical method for assaying the atropine in the leaves. In this study, a faster, solvent-saving, and more reliable method for quality control of A. belladonna samples was developed. Ultrasound-assisted extraction was proposed and optimized by fractional factorial design followed by Box-Behnken design. For modeling atropine content, the following optimal conditions were established: particle size, 180 µm; percentage methanol in water, 50%; volume of solvent, 15 ml; time of extraction, 60 min; and number of extractions, two. This led to a significant improvement in atropine extraction (P < 0.001). For cleanup, solid-phase extraction was used as an alternative to liquid-liquid extraction, giving similar results, with higher reproducibility. Finally, for the atropine assay, a UPLC method was validated as a substitute for the classic titration method. Taken together, the development of an ultrasound-assisted extraction-solid-phase extraction-UPLC approach allowed the determination of atropine content in A. belladonna leaves in a time- and solvent-saving manner, with high reliability.

Bioactive Azepine-Indole Alkaloids from Psychotria nemorosa.

Phytochemical investigation of the alkaloid extract of the aerial parts of Psychotria nemorosa led to the isolation and characterization of 10 azepine-indole alkaloids, i.e., cimitrypazepine (1), fargesine (2), nemorosines A (3), and B (12), nemorosinosides A-F (4-9), as well as two ß-carboline derivatives, 10-hydroxyisodolichantoside (10) and 10-hydroxydolichantoside (11), an isoxazole alkaloid, nemorosinoside G (13), serotonin (14), bufotenine (15), and (S)-gentianol (16). Compounds 3-13 have not yet been described. These compounds were isolated by semipreparative HPLC, and their structures were determined by means of HRMS, NMR, and ECD measurements. In addition, the monoamine oxidase-A (MAO-A), MAO-B, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitory activities were evaluated. Alkaloids 1-3 inhibited the MAO-A activity with IC50 values of 1.4, 1.4, and 0.9 µM, respectively.

The Protective Potential of Phyllanthus niruri and Corilagin on Gastric Lesions Induced in Rodents by Different Harmful Agents.

The gastroprotective effect of the methanol extract of Phyllantus niruri and its main constituent, corilagin, were studied in vivo. The extract (50, 125, or 250 mg/kg, p. o.) inhibited ethanol-induced lesions in rats by 43 % (p < 0.001), 69 % (p < 0.001), and 99 % (p < 0.001), respectively. It also inhibited the formation of indomethacin-induced gastric ulcers in rats by 80 % (p < 0.01), 89 % (p < 0.01), and 97 % (p < 0.01). A decrease in lipid hydroperoxide levels (p < 0.01) and in myeloperoxidase activity (p < 0.05) evidenced a reduction of oxidative damage and neutrophil infiltration in gastric tissues from ulcerated mice using ethanol/HCl. Potent in vitro free radical scavenger activity (IC50 = 0.07) using the DPPH assay was observed. In contrast, the extract (250 mg/kg, i. d.) did not show antisecretory activity in pylorus-ligated rats, and also failed to inhibit the H+,K+-ATPase activity in vitro. However, in pylorus-ligated rats, the extract (50, 125, and 250 mg/kg, i. d.) increased adhered mucus content by 22 % (p < 0.05), 28 % (p < 0.01), and 38 % (p < 0.01), respectively. The involvement of prostaglandins, nonprotein endogenous sulfhydryl compounds, α2-receptors, and endogenous nitric oxide in the gastroprotection elicited by the extract was also evaluated. Finally, corilagin reduced the lesion area of ethanol-induced gastric ulcers in mice by 88 % (30 mg/kg, p. o.; p < 0.001). Based on these results, it has been concluded that P. niruri methanol extract possesses gastroprotective activity by different and complementary pathways, which together promote an improvement in gastric cytoprotection. The presence of corilagin may partially explain the effectiveness of the extract against gastric damage.

Hypolipemic effect of Garcinia cambogia in obese women.

Garcinia cambogia seems to promote weight reduction and improvement on lipid profile by its major compound, hydroxycitric acid (HCA), blocking ATP-citratelyase, potentially inhibiting lipogenesis. Furthermore, it is suggested that its extract is able to change the adipokine levels. Thus, the aim of this study was to analyse the effect of G. cambogia on the lipid profile, endocrine, calorimetric and anthropometric parameters of obese women. The women (BMI > 25 kg/m(2) ; age 25-60 years), divided in treated (n = 30) and control (n = 13) groups, received 2.4 g (800 mg 3×/day) of garcinia extract (50% of HCA) or placebo during 60 days, respectively, as well as dietary control. Weight, BMI, waist-hip ratio and percentage of fat mass, resting metabolic rate, respiratory coefficient, triglycerides (TG), total cholesterol, HDL and LDL, leptin and insulin serum levels were evaluated. TG was significantly reduced in the treated group (p = 0.0002) and the post-treatment variation was different compared to the placebo group (p = 0.04). No significant response was observed on other variables of the lipid profile, or on the anthropometric and calorimetric parameters. Leptin and insulin levels did not change significantly after the treatment. The short-term treatment with G. cambogia demonstrated a hypotriglyceridemic effect, which does not appear to be related to changes in leptinemia.

Antihyperalgesic activity of the methanol extract and some constituents obtained from Polygala cyparissias (Polygalaceae).

Polygala cyparissias, used in folk medicine as an anaesthetic, has already demonstrated antinociceptive activity against acute pain. In this study, we investigated the antihyperalgesic activity of the P. cyparissias methanol extract (PCME) from which the following compounds were isolated: α-spinasterol (PC1), 1,3-dihydroxy-7-methoxyxanthone (PC2), 1,7-dihydroxy-2,3-methylenedioxyxanthone (PC3) and 1,3,6,8-tetrahydroxy-2,7-dimethoxyxanthone (PC4). The antihyperalgesic effect was evaluated using experimental models of persistent pain induced by carrageenan, lipopolysaccharide (LPS), Freund's Complete Adjuvant (CFA), PGE(2) or epinephrine. The partial ligation of the sciatic nerve (PLSN) model was also used. In inflammatory hyperalgesia induced by carrageenan, LPS, CFA or PGE(2), the inhibition values obtained with the PCME treatment were 68 ± 3%, 89 ± 5%, 43 ± 3% and 40 ± 4%, respectively. In epinephrine-induced hyperalgesia, the extract was effective, reducing 99 ± 11% of response frequency, while in PLSN, 54 ± 4% of inhibition was obtained. These results allow to suggest that the antihyperalgesic activity of PCME is, at least in part, related to its capability to inhibit the hypersensitization induced by pro-inflammatory mediators, such as LPS, carrageenan and CFA, without interfering with locomotor activity or motor performance. Furthermore, compounds PC1, PC3 and PC4 inhibited the carrageenan-induced hyperalgesia with inhibition of 42 ± 6%, 48 ± 5% and 64 ± 4%, respectively. In summary, our data demonstrate that PCME has relevant antihyperalgesic activity and that the isolated PC1, PC3 and PC4 seem to be responsible, at least in part, for this important effect.