**1. Introduction**

Benign prostatic hyperplasia (BPH) refers to the progressive enlargement of the prostate gland and is one of the most common diseases in the aging male population. Approximately, half of men over 50 years of age develop BPH [1]. BPH is usually accompanied by lower urinary tract symptoms and related complications such as urinary frequency, urinary retention, and urinary tract infection, which may lead to a decrease in the quality of life and even cause extreme annoyance and embarrassment. BPH is typically treated with pharmacological intervention or surgery [2].

Notwithstanding, the first treatment option for many BPH patients is still pharmacological therapies, among which the main classes of medicine include 5α-reductase inhibitors and α-adrenergic blockers are currently used for symptom relief [3]. However, the adverse side effects of these traditional medications, such as retrograde ejaculation, orthostatic hypotension, and erectile dysfunction, which affects many patients, remain a major challenge [4]. Therefore, it is necessary to search for and use "safer" and effective alternatives against BPH.

Carotenoid astaxanthin (AST) is a red-orange pigment primarily found in organisms, such as shrimp, algae, fish, and crustaceans, containing two oxygenated ends on each tail of the structure (Figure 1) [5,6]. This natural dietary carotenoid has a variety of functions,

**Citation:** Wang, L.; Hou, Y.; Wang, R.; Pan, Q.; Li, D.; Yan, H.; Sun, Z. Inhibitory Effect of Astaxanthin on Testosterone-Induced Benign Prostatic Hyperplasia in Rats. *Mar. Drugs* **2021**, *19*, 652. https:// doi.org/10.3390/md19120652

Academic Editors: Hayato Maeda and Masashi Hosokawa

Received: 15 October 2021 Accepted: 17 November 2021 Published: 23 November 2021

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including antioxidant, anti-inflammatory, and antitumor properties [7–10]. Moreover, a previous study demonstrated that AST might be safe and well tolerated in rats [11].

Rat prostate mainly consists of paired ventral lobes and paired dorsal lobes [12]. Each lobe is composed of acini, lined by a single epithelium layer and separated by connective tissues containing stromal cells [12,13]. Prostate growth may be stimulated by the continued presence of certain hormones such as testosterone (T) [14]. Dihydrotestosterone (DHT), which is the most active and principal androgen in the prostate, is synthesized from T by the enzyme 5 α-reductase. Therefore, the activity of enzyme 5 α-reductase, whose isoform 2 predominates in the prostate, may play an important role in the pathogenesis and progression of BPH. Research has suggested that low levels of AST can inhibit 5 α-reductase significantly in vitro [15].

Moreover, AST may have an inhibitory effect on prostate cancer. Studies have indicated that AST can modulate the proliferation and apoptosis of cells and inhibit PC-3 xenograft prostate tumors in nude mice [10]. Research has also shown that AST can inhibit the proliferation of aggressive PCa DU145 cells [16].

However, to the best of our knowledge, there is no evidence of the efficacy of AST on BPH in vivo. In the present study, we investigated whether AST could inhibit the development of T-induced BPH in rats.

**Figure 1.** Chemical structure of astaxanthin [7].
