Gains in Fujifilm Holdings Corp and Kao Corp after their quarterly earnings helped cap losses.
The benchmark Nikkei ended 0.4 percent lower at 13,799.35, down for third straight session.
It rallied nearly 12 percent last month, marking its best April performance since 1993 and a ninth straight month of gains - its longest such winning streak since May 2005 to January 2006.
"The fundamental view (on corporate profit growth) is still sluggish," said Shun Maruyama, chief Japan equity strategist at BNP Paribas.
"The market has already priced in the effect of the currency weakness. If we exclude the currency weakness, companies are still bearish in the economic recovery forecast for the current term and the next."
"In the shorter-term, we have no choice but to recommend to take profits," he said, but added that he remained upbeat on the Nikkei and expected the benchmark to hit 15,000 by year-end.
Expectations that Japanese firms would sharply raise their earnings forecast for this fiscal year ending March had been high after the yen weakened 21 percent since mid-November, when Shinzo Abe, who became Prime Minister in December, promised expansionary monetary and fiscal policies to revive the economy.
During the same period, the Nikkei index has rallied nearly 60 percent. Japanese equities carry a 12-month forward price-to-earnings ratio of 15.1, a level not seen since May 2010 but still below its 10-year average of 16.4, data from Thomson Reuters Datastream showed.
Investors will keep an eye on the outcome of the U.S. Federal Reserve's two-day policy meeting later in the day.
STRUGGLING SHARP
Sharp sagged 5 percent on news that the liquid crystal display maker was expected to post a worse than forecast 500 billion yen net loss in the year that ended March 31. Sources with knowledge of the earnings result confirmed a report by the Nikkei newspaper to Reuters on Wednesday.
Tokyo Electron dropped 4.1 percent after it forecast an operating profit of 18 billion yen for the fiscal year through March, coming in below an average of 21 billion yen from 18 analysts polled by Thomson Reuters I/B/E/S.
Japan Airlines also disappointed investors with its earnings guidance for the current business year. Its stock lost 4.4 percent after hitting its highest level since relisting in September in the previous session.
"I clearly don't see these forecasts are catalysts for investors to go crazy on Japan," a senior dealer at a foreign bank said.
"But the conservative guidance leaves room for revision if the FX is maintained at this level, or the yen gets weaken."
PROFIT-TAKING ON SOFTBANK, NOMURA
Other notable decliners included SoftBank Corp, which fell 1.7 percent as investors took profit on the mobile operator after it hit a seven-year high on Tuesday before it announced results which were largely in line with expectations.
Investors also cashed in on Japan's top brokerage Nomura Holdings after climbing 4.5 percent in the previous session after strong quarterly results. The stock was down 2.5 percent and the most traded stock on the main board by turnover.
The broader Topix index fell 0.6 percent to 1,158.37, with trading volume hitting a four-week low at 3.07 billion shares.
Still, there are encouraging signs in the corporate sector. Of the 57 companies that have reported quarterly figures as of Tuesday, 53 percent of them either beat or met market expectations, according to Thomson Reuters StarMine. That compared with 38 percent in the previous quarter.
Fujifilm jumped 6.6 percent after its operating profit came in slightly above its own forecast for the year ended March, while its forecast for the current business year was a touch ahead of market consensus.
Kao Corp was the fifth top-weighted gainer, up 2.5 percent after its first quarter earnings.
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