Three undescribed dimeric pyridine-containing alkaloids, caryopterisines C - E, and four unreported cyclopenta[c]pyridine-derived alkaloids, caryopterisines F - I, were identified from Caryopteris glutinosa Rehder (Lamiaceae), together with two known monoterpene alkaloids. Caryopterisine C, featuring with an unprecedented 6/5/6/6/5 pentacyclic rings scaffold, may biosynthetically stem from a Diels-Alder reaction of two cyclopenta[c]pyridine-containing monomers and a following aromatization rearrangement reaction. Caryopterisines D and E, possessing an unprecedented 6/6/6/6/5 fused rings framework, may originate from a same Diels-Alder reaction of two monomers and subsequent aromatization arrangement, Baeyer-Villiger oxidation, and a set of tailoring reactions. Caryopterisine C showed strong inhibition on collagen accumulation in NIH3T3 cells (IC(50) = 14.26 +/- 1.46 muM). Caryopterisines G and I reduce collagen accumulation with IC(50) values 88.91 +/- 0.95 muM and 33.09 +/- 1.38 muM, respectively. The Western blotting of the transforming growth factor-beta-activated signaling pathways revealed that caryopterisine C inhibits collagen expression and accumulation via suppression of the phosphorylation of ERK1/2, P38, and SMAD2/3. The present works indicate caryopterisine C is a potential lead compound for the development of antifibrotic drugs. CI - Copyright (c) 2022 Elsevier Ltd. All rights reserved.