Protium heptaphyllum (Aubl.) Marchand (PH) trees are endemic to the tropical region of South America, mostly Brazil. Antibacterial, antinociceptive, anti-inflammatory, anxiolytic, antidepressant and anti-hyperlipidemic/anti-hypercholesterolemic effects were reported for its resinous exudate Protium heptaphyllum resin (PHR).
This work aims to provide a qualitative and quantitative consistent chemical profiling of the major constituents of this resin and two extracts enriched in acid (acidic triterpene concentrated extract, ATCE) and neutral triterpenes (α and β-amyrin concentrated extract, AMCE).
GC–MS/GC–FID was used for volatile terpene fraction, a validated GC–MS method was developed for quantification of neutral α and β-amyrin and HPLC–APCI HRMS2 was used for acidic triterpenes analysis. The chemical investigation reported 29 molecules, including 14 volatile terpenes, 6 neutral triterpenes and 11 acid triterpenes. The most abundant compounds were α-amyrin
(251.28 g kg−1, 123.98 g kg−1 and 556.82 g kg−1 in PHR, ATCE and AMCE, respectively), β-amyrin (172.66 g kg−1, 95.39 g kg−1 and 385.58 g kg−1 in PHR, ATCE and AMCE, respectively), 3-oxo-tirucalla-7,24-dien-21-oic acid (80.64 g kg−1, 157.10 g kg−1 and 15.31 g kg−1 in PHR, ATCE
and AMCE, respectively) and 3α-hydroxy-tirucalla-8,24-dien-21-oic acid (77.71 g kg−1, 130.40 g kg−1 and 11.64 g kg−1 in PHR, ATCE Results showed specific enrichment of acidic and neutral triterpenoids in the two respective extracts.

Geddo F., Scandiffio R., Antoniotti S., Cottone E., Querio G., Maffei M. E. 2, Bovolin P. 1 and Gallo M. P.
PipeNig®-FL, a Fluid Extract of Black Pepper (Piper Nigrum L.) with a High Standardized Content of Trans-β-Cariofillene, Reduces Lipid Accumulation in 3T3-L1 Preadipocytes and Improves Glucose Uptake in C2C12 Myotubes.
Nutrients 11.11 (2019): 2788.

Hypercholesterolemia is one of the major causes of cardiovascular disease, the risk of which is further increased if other forms of dyslipidemia occur. Current therapeutic strategies include changes in lifestyle coupled with drug administration. Statins represent the most common therapeutic approach, but they may be insufficient due to the onset of resistance mechanisms and side effects. Consequently, patients with mild hypercholesterolemia prefer the use of food supplements since these are perceived to be safer. Here, we investigate the phytochemical profile and cholesterol-lowering potential of Protium heptaphyllum gum resin extract (PHE). Chemical characterization via HPLC-APCI-HRMS2 and GC-FID/MS identified 13 compounds mainly belonging to ursane, oleanane, and tirucallane groups. It was initially evaluated the variation of gene expression, via realtime PCR, of genes involved in the metabolism (biosynthesis and catabolism) of cholesterol and lipid metabolism. Studies on human hepatocytes have revealed how PHE is able to reduce cholesterol production and regulate the expression of proteins involved in its metabolism. (HMGCR, PCSK9, LDLR, FXR, IDOL, and PPAR). Moreover, measuring the inhibitory activity of PHE against HMGR, moderate inhibition was recorded. Finally, molecular docking studies identified acidic tetra- and pentacyclic triterpenoids as the main compounds responsible for this action. These experimental evaluations were conducted by comparing the action of Protium extract with the metabolically active form of lovastatin. These experimental evaluations were conducted by comparing the action of Protium extract with the metabolically active form of lovastatin. However, the mechanism of action does not appear to be directly related to the inhibition of the enzyme HMGR with a statin-like mechanism since the Protium extract showed a moderate inhibition of the aforementioned enzyme (Fig.3). Finally, molecular docking studies have identified tetra and pentacyclic acid triterpenoids as the main responsible for this action. In conclusion, our study demonstrates how PHE may be a useful alternative to contrast hypercholesterolemia, highlighting its potential as a sustainable multitarget natural extract for the nutraceutical industry that is rapidly gaining acceptance as a source of health-promoting compounds.

Mannino G., Iovino P., Lauria A., Genova T., Asteggiano A., Notarbartolo M., Porcu A., Serio G., Chinigò G., Occhipinti A., Capuzzo A., Medana C., Munaron L., Gentile C. (2021)
Bioactive Triterpenes of Protium heptaphyllum Gum Resin Extract Display Cholesterol-Lowering Potential
FormaInt. J. Mol. Sci. 2021, 22(5), 2664